60 results on '"J. Bart A. Crusius"'
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2. Farnesoid X receptor (FXR) activation and FXR genetic variation in inflammatory bowel disease.
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Rian M Nijmeijer, Raffaella M Gadaleta, Saskia W C van Mil, Adriaan A van Bodegraven, J Bart A Crusius, Gerard Dijkstra, Daan W Hommes, Dirk J de Jong, Pieter C F Stokkers, Hein W Verspaget, Rinse K Weersma, C Janneke van der Woude, Janneke M Stapelbroek, Marguerite E I Schipper, Cisca Wijmenga, Karel J van Erpecum, Bas Oldenburg, and Dutch Initiative on Crohn, Colitis (ICC)
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Medicine ,Science - Abstract
BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients.
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- 2011
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3. Correction: Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms.
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Alienke J. Monsuur, Paul I. W. de Bakker, Alexandra Zhernakova, Dalila Pinto, Willem Verduijn, Jihane Romanos, Renata Auricchio, Ana Lopez, David A. van Heel, J. Bart A Crusius, and Cisca Wijmenga
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Medicine ,Science - Published
- 2009
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4. Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.
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Alienke J Monsuur, Paul I W de Bakker, Alexandra Zhernakova, Dalila Pinto, Willem Verduijn, Jihane Romanos, Renata Auricchio, Ana Lopez, David A van Heel, J Bart A Crusius, and Cisca Wijmenga
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Medicine ,Science - Abstract
BACKGROUND: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. METHODOLOGY: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. CONCLUSION: Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.
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- 2008
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5. Brief Report: The Role of Rare Protein‐Coding Variants in Anti–Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis
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João Eurico Fonseca, Michelle O'Laughlin, Catrina Fronick, Yukinori Okada, Robert S. Fulton, Soumya Raychaudhuri, Tom W J Huizinga, Eli A. Stahl, Dimitrios A. Pappas, Robert M. Plenge, Peter K. Gregersen, Gertjan Wolbink, Joel M. Kremer, Jeff Greenberg, Corinne Miceli-Richard, David E. Larson, Niek de Vries, Dorothée Diogo, Tracie L. Deluca, Michael T. Nurmohamed, Paul P. Tak, Lucinda Fulton, Anne Barton, Fina A S Kurreeman, Elizabeth W. Karlson, Annette Lee, Helena Canhão, Marieke J H Coenen, Elaine R. Mardis, Xavier Mariette, Irene E. van der Horst-Bruinsma, Jing Cui, J. Bart A. Crusius, Clinical Immunology and Rheumatology, AII - Inflammatory diseases, Amsterdam institute for Infection and Immunity, and Experimental Immunology
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Male ,0301 basic medicine ,Necrosis ,Immunology ,Alpha (ethology) ,Bioinformatics ,Article ,Arthritis, Rheumatoid ,Open Reading Frames ,03 medical and health sciences ,Text mining ,Rheumatology ,medicine ,Humans ,Immunology and Allergy ,Coding region ,Gene ,Tumor Necrosis Factor-alpha ,business.industry ,Genetic Variation ,Middle Aged ,medicine.disease ,Phenotype ,Treatment Outcome ,030104 developmental biology ,Rheumatoid arthritis ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Female ,Tumor necrosis factor alpha ,medicine.symptom ,business - Abstract
Item does not contain fulltext OBJECTIVE: In many rheumatoid arthritis (RA) patients, disease is controlled with anti-tumor necrosis factor (anti-TNF) biologic therapies. However, in a significant number of patients, the disease fails to respond to anti-TNF therapy. We undertook the present study to examine the hypothesis that rare and low-frequency genetic variants might influence response to anti-TNF treatment. METHODS: We sequenced the coding region of 750 genes in 1,094 RA patients of European ancestry who were treated with anti-TNF. After quality control, 690 genes were included in the analysis. We applied single-variant association and gene-based association tests to identify variants associated with anti-TNF treatment response. In addition, given the key mechanistic role of TNF, we performed gene set analyses of 27 TNF pathway genes. RESULTS: We identified 14,420 functional variants, of which 6,934 were predicted as nonsynonymous 2,136 of which were further predicted to be "damaging." Despite the fact that the study was well powered, no single variant or gene showed study-wide significant association with change in the outcome measures disease activity or European League Against Rheumatism response. Intriguingly, we observed 3 genes, of 27 with nominal signals of association (P < 0.05), that were involved in the TNF signaling pathway. However, when we performed a rigorous gene set enrichment analysis based on association P value ranking, we observed no evidence of enrichment of association at genes involved in the TNF pathway (Penrichment = 0.15, based on phenotype permutations). CONCLUSION: Our findings suggest that rare and low-frequency protein-coding variants in TNF signaling pathway genes or other genes do not contribute substantially to anti-TNF treatment response in patients with RA.
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- 2017
6. In Memoriam of Prof. Bing Xia, MD, PhD
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Guoying Zhou, Weixi Xia, A. Salvador Peña, Jing Wu, J. Bart A. Crusius, Jun Sun, Servaas A. Morré, Harry Xia, Juei-Tang Cheng, and Qin Ouyang
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- 2015
7. Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations†
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Colin L. Noble, Roel Heijmans, Tony R. Merriman, J. Bart A. Crusius, Javier Martin, A. Salvador Peña, Jade E Hollis-Moffatt, Eleonora A. M. Festen, Simone C. Wolfkamp, Rogelio Palomino-Morales, Antonio Nieto, Rebecca L. Roberts, María Gómez-García, Richard B. Gearry, Cisca Wijmenga, Bobby P. C. Koeleman, Rinse K. Weersma, Adriaan A. van Bodegraven, Murrary L. Barclay, Timothy R D J Radstake, Luis Rodrigo, Pieter C. F. Stokkers, Miguel A. López-Nevot, Behrooz Z. Alizadeh, Sander Meisneris, Tytgat Institute for Liver and Intestinal Research, Gastroenterology and Hepatology, Gastroenterology and hepatology, Pathology, CCA - Immuno-pathogenesis, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Life Course Epidemiology (LCE)
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Genotype ,NEW-ZEALAND ,Genome-wide association study ,FCGR2A ,Auto-immunity, transplantation and immunotherapy [N4i 4] ,Polymorphism, Single Nucleotide ,FcgR2a ,AUTOIMMUNE-DISEASES ,Inflammatory bowel disease ,Linkage Disequilibrium ,White People ,Cohort Studies ,FcgR3a ,Crohn Disease ,Humans ,Immunology and Allergy ,Medicine ,Genetic Predisposition to Disease ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,GENOME-WIDE ASSOCIATION ,Health care ethics [NCEBP 5] ,Netherlands ,ulcerative colitis ,TOLL-LIKE RECEPTORS ,Crohn's disease ,genome-wide association study ,business.industry ,Receptors, IgG ,CIRCULATING IMMUNE-COMPLEXES ,Gastroenterology ,Case-control study ,Odds ratio ,medicine.disease ,ACTIVE CROHNS-DISEASE ,Ulcerative colitis ,digestive system diseases ,RHEUMATOID-ARTHRITIS ,Phenotype ,ULCERATIVE-COLITIS ,Evaluation of complex medical interventions [NCEBP 2] ,Spain ,Case-Control Studies ,Immunology ,Colitis, Ulcerative ,GAMMA RECEPTOR-IIA ,business ,New Zealand - Abstract
Item does not contain fulltext BACKGROUND: The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand. RESULTS: In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MH] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations. CONCLUSIONS: The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC. 01 december 2010
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- 2010
8. Analysis of SNPs with an effect on gene expression identifies UBE2L3 and BCL3 as potential new risk genes for Crohn's disease
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Karin Fransen, Jinyuan Y. Fu, Adriaan A. van Bodegraven, Pieter Zanen, Daniel W. Hommes, J. Bart A. Crusius, Cleo C. van Diemen, Eleonora A. M. Festen, Rinse K. Weersma, Marijn C. Visschedijk, Cisca Wijmenga, Suzanne van Sommeren, Pieter C. F. Stokkers, Dirk J. de Jong, Lude Franke, Gastroenterology and hepatology, CCA - Disease profiling, Pathology, Gastroenterology and Hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Male ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,PATHOGENESIS ,Gene Expression ,Genome-wide association study ,Single-nucleotide polymorphism ,Disease ,Biology ,Quantitative trait locus ,VARIANTS ,Polymorphism, Single Nucleotide ,White People ,Cohort Studies ,Crohn Disease ,B-Cell Lymphoma 3 Protein ,Proto-Oncogene Proteins ,Molecular genetics ,Genetics ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Molecular gastro-enterology and hepatology [IGMD 2] ,GENOME-WIDE ASSOCIATION ,Molecular Biology ,Gene ,Genetics (clinical) ,genome-wide association inflammatory-bowel-disease susceptibility loci variants pathogenesis ,Genetic association ,General Medicine ,Case-Control Studies ,Ubiquitin-Conjugating Enzymes ,Female ,Genome-Wide Association Study ,Transcription Factors ,INFLAMMATORY-BOWEL-DISEASE - Abstract
Item does not contain fulltext Genome-wide association studies (GWAS) for Crohn's disease (CD) have identified loci explaining approximately 20% of the total genetic risk of CD. Part of the other genetic risk loci is probably partly hidden among signals discarded by the multiple testing correction needed in the analysis of GWAS data. Strategies for finding these hidden loci require large replication cohorts and are costly to perform. We adopted a strategy of selecting SNPs for follow-up that showed a correlation to gene expression [cis-expression quantitative trait loci (eQTLs)] since these have been shown more likely to be trait-associated. First we show that there is an overrepresentation of cis-eQTLs in the known CD-associated loci. Then SNPs were selected for follow-up by screening the top 500 SNP hits from a CD GWAS data set. We identified 10 cis-eQTL SNPs. These 10 SNPs were tested for association with CD in two independent cohorts of Dutch CD patients (1539) and healthy controls (2648). In a combined analysis, we identified two cis-eQTL SNPs that were associated with CD rs2298428 in UBE2L3 (P=5.22x10(-5)) and rs2927488 in BCL3 (P=2.94x10(-4)). After adding additional publicly available data from a previously reported meta-analysis, the association with rs2298428 almost reached genome-wide significance (P=2.40x10(-7)) and the association with rs2927488 was corroborated (P=6.46x10(-4)). We have identified UBE2L3 and BCL3 as likely novel risk genes for CD. UBE2L3 is also associated with other immune-mediated diseases. These results show that eQTL-based pre-selection for follow-up is a useful approach for identifying risk loci from a moderately sized GWAS.
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- 2010
9. Distribution of peroxisome proliferator–activated receptor–gamma polymorphisms in Chinese and Dutch patients with inflammatory bowel disease
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Feng Zhou, Ouafae Karimi, Jun Xiao, Bing Xia, Servaas A. Morré, Zhongli Wang, Zhitao Chen, Hongling Wang, Umid Kumar Shrestha, Jin Li, J. Bart A. Crusius, A.A. van Bodegraven, Pathology, Gastroenterology and hepatology, and CCA - Disease profiling
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Adult ,Male ,China ,medicine.medical_specialty ,Genotype ,Population ,Disease ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Gastroenterology ,Inflammatory bowel disease ,White People ,Asian People ,Gene Frequency ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,SNP ,Genetic Predisposition to Disease ,education ,Genetic Association Studies ,Netherlands ,education.field_of_study ,business.industry ,Odds ratio ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,PPAR gamma ,Phenotype ,Immunology ,Etiology ,Colitis, Ulcerative ,Female ,business - Abstract
Background: As peroxisome proliferator–activated receptor–gamma (PPAR-γ) is frequently expressed in colon, its genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD). The aims of the present study were to determine the distribution of PPAR-γ polymorphisms Pro12Ala and C161T and to explore the association between the PPAR-γ genotypes and phenotypes of IBD patients. Methods: A total of 244 IBD patients [212 ulcerative colitis (UC) and 32 Crohn's disease (CD)] and 220 controls in the Chinese population and 603 IBD patients (302 UC and 301 CD) and 180 controls in the white Dutch population were enrolled in the study. The phenotypes of Chinese IBD patients were grouped according to disease location. The PPAR-γ polymorphisms Pro12Ala and C161T were genotyped by PCR-based methods. Results: In the Chinese population, T carriers of the PPAR-γ C161T polymorphism were more common in UC patients than in the controls [37.7% vs. 25.5%, odds ratio 1.77, 95% confidence interval 1.18–2.68, P = 0.007], whereas Ala carriers of the Pro12Ala polymorphism showed no significant association in UC patients, but there was a significant association of Ala carriers with more extensive disease among the UC patients (P = 0.002); Pro12Ala and C161T genotypes did not show any associations with CD patients. No associations were found for the PPAR-γ C161T SNP studied in the Dutch IBD population. Conclusions: Our study showed the potential association between the PPAR-γ C161T polymorphism and UC patients in the central Chinese population. This finding was not replicated in the Dutch population. Further studies are necessary to explore the functional implication of the PPAR-γ C161T polymorphism in Chinese UC patients. (Inflamm Bowel Dis 2009;)
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- 2010
10. Prospective Human Leukocyte Antigen, Endomysium Immunoglobulin A Antibodies, and Transglutaminase Antibodies Testing for Celiac Disease in Children with Down Syndrome
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Jeroen Wouters, J. Bart A. Crusius, Marco W.J. Schreurs, Laura R. de Baaij, Chantal J.M. Broers, Michel E. Weijerman, Reinoud J. B. J. Gemke, A. Marceline van Furth, B. Mary E. von Blomberg, Pediatric surgery, Pathology, Gastroenterology and hepatology, CCA - Disease profiling, and ICaR - Ischemia and repair
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Adult ,Male ,Heterozygote ,Down syndrome ,Adolescent ,Duodenum ,Biopsy ,Buccal swab ,Human leukocyte antigen ,Serology ,Young Adult ,HLA Antigens ,HLA-DQ Antigens ,medicine ,Humans ,Mass Screening ,Prospective Studies ,Intestinal Mucosa ,Child ,Mass screening ,Autoantibodies ,Transglutaminases ,biology ,medicine.diagnostic_test ,business.industry ,Homozygote ,Infant ,nutritional and metabolic diseases ,medicine.disease ,Endomysium ,Immunoglobulin A ,Celiac Disease ,Early Diagnosis ,medicine.anatomical_structure ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Feasibility Studies ,Female ,Down Syndrome ,Antibody ,business - Abstract
Objective To assess the effect of a prospective screening strategy for the early diagnosis of celiac disease (CD) in children with Down syndrome (DS). Study design Blood samples were taken from 155 children with DS. Buccal swabs were also taken from 9 of these children for determination of human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 positivity. Independently, immunoglobulin A anti-endomysium-(EMA) and anti-tissue transglutaminase antibodies (TGA) were tested. An intestinal biopsy was performed to confirm the diagnosis of CD. Results Sixty-three children (40.6%) had test results that were positive for HLA-DQ2 or HLA-DQ8. Results of HLA DQ-typing of DNA isolated from blood and buccal swabs were identical. Eight of the children in whom test results were positive for HLA-DQ2/8 also had positive test results for EMA and TGA. CD was confirmed in 7 of these children with an intestinal biopsy, and in 1 child, CD was suggested with improvement on a gluten-free diet. Conclusions We found a prevalence of CD in children with DS of 5.2% (10 times higher than the general Dutch population). We recommend HLA-DQ2/8 typing from buccal swabs in the first year of life and initiating serologic screening of children with DS in whom test results are positive for HLA-DQ2 or DQ8 at age 3 years. Early knowledge of negative HLA-DQ2/8 status can reassure most parents that their children do not have a CD risk.
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- 2009
11. Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP
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Alienke J. Monsuur, Cisca Wijmenga, Alexandra Zhernakova, Gosia Trynka, Rian M. Nijmeijer, Ruben van 't Slot, Adriaan A. van Bodegraven, Lude Franke, Marianna Bevova, E Festen, Pieter C. F. Stokkers, Roel Heijmans, J. Bart A. Crusius, H. Marike Boezen, Rinse K. Weersma, David A. van Heel, Cleo C. van Diemen, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Gastroenterology and Hepatology, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Gastroenterology and hepatology, CCA - Disease profiling, and Pathology
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Male ,EXPRESSION ,Linkage disequilibrium ,Population ,PATHOGENESIS ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,ADAPTER PROTEIN CARD9 ,Inflammatory bowel disease ,Linkage Disequilibrium ,Crohn Disease ,Report ,Genetics ,medicine ,RISK VARIANTS ,Humans ,SNP ,Genetics(clinical) ,Genetic Predisposition to Disease ,Interleukin-18 Receptor beta Subunit ,GENOME-WIDE ASSOCIATION ,education ,Genetics (clinical) ,POPULATION ,TOLL-LIKE RECEPTORS ,Crohn's disease ,education.field_of_study ,medicine.disease ,Ulcerative colitis ,Immunity, Innate ,digestive system diseases ,CARD Signaling Adaptor Proteins ,Immunology ,CELLS ,Colitis, Ulcerative ,Female ,IL-18 ,INFLAMMATORY-BOWEL-DISEASE - Abstract
The two main phenotypes of inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--are chronic intestinal inflammatory disorders with a complex genetic background. Using a three-stage design, we performed a functional candidate-gene analysis of innate immune pathway in IBD. In phase I, we typed 354 SNPs from 85 innate immunity genes in 520 Dutch IBD patients (284 CD, 236 UC) and 808 controls. In phase II, ten autosomal SNPs showing association at p < 0.006 in phase I were replicated in a second cohort of 545 IBD patients (326 CD, 219 UC) and 360 controls. In phase III, four SNPs with p < 0.01 in the combined phase I and phase II analysis were genotyped in an additional 786 IBD samples (452 CD, 334 UC) and 768 independent controls. Joint analysis of 1851 IBD patients (1062 CD, 789 UC) and 1936 controls demonstrated strong association to the IL18RAP rs917997 SNP for both CD and UC (p(IBD) 1.9 x 10(-8); OR 1.35). Association in CD is independently supported by the Crohn's disease dataset of the Wellcome Trust Case Control Consortium (imputed SNP rs917997, p = 9.19 x 10(-4)). In addition, an association of the CARD9 rs10870077 SNP to CD and UC was observed (p(IBD) = 3.25 x 10(-5); OR 1.21). Both genes are located in extended haplotype blocks on 2q11-2q12 and 9q34.3, respectively. Our results indicate two IBD loci and further support the importance of the innate immune system in the predisposition to both CD and UC.
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- 2008
12. Common variants at CD40 and other loci confer risk of rheumatoid arthritis
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Robert M. Plenge, J. Bart A. Crusius, Niek de Vries, Soumya Raychaudhuri, Mark Seielstad, Tom W J Huizinga, Ann B. Begovich, Lars Klareskog, Peter K. Gregersen, Benjamin D. Korman, René E. M. Toes, Elizabeth W. Karlson, Annette Lee, Lindsey A. Criswell, Monica Chang, Candace Guiducci, Sandra Wong, Nancy A. Shadick, Karen H. Costenbader, Joseph J. Catanese, Michael F. Seldin, David Altshuler, Lauren Gianniny, Daniel L. Kastner, Elaine F. Remmers, Jane Worthington, Paul P. Tak, Annette H M van der Helm-van Mil, Michael E. Weinblatt, Kristin G. Ardlie, Jing Cui, Rachel Hackett, Fina A S Kurreeman, Gertjan Wolbink, Mark J. Daly, Benjamin M. Neale, Bo Ding, Irene E. van der Horst-Bruinsma, Jonathan S. Coblyn, Lars Alfredsson, Christopher I. Amos, Noël P. Burtt, Leonid Padyukov, Rheumatology, CCA - Disease profiling, Pathology, AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, and Landsteiner Laboratory
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PRKCQ ,Genetic Linkage ,Single-nucleotide polymorphism ,Locus (genetics) ,Biology ,TNFAIP3 ,Polymorphism, Single Nucleotide ,Article ,Arthritis, Rheumatoid ,Genetic linkage ,Genetics ,medicine ,Chromosomes, Human ,Humans ,Genetic Predisposition to Disease ,CD40 Antigens ,Gene ,Genome, Human ,Haplotype ,Chromosome Mapping ,medicine.disease ,Haplotypes ,Rheumatoid arthritis ,Case-Control Studies ,Immunology - Abstract
To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).
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- 2008
13. Serological Screening for Celiac Disease in Adult Chinese Patients With Diarrhea Predominant Irritable Bowel Syndrome
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Guifang Yang, A. Salvador Peña, Hongling Wang, Bing Xia, Ji-guang Kou, Jing Wu, Linjie Luo, Anlong Yuan, Min Wang, Servaas A. Morré, J. Bart A. Crusius, Guoying Zhou, B. Mary E. von Blomberg, Pathology, Medical Microbiology and Infection Prevention, and CCA - Disease profiling
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Adult ,Male ,medicine.medical_specialty ,China ,Genotype ,Duodenum ,Observational Study ,Comorbidity ,Asymptomatic ,Gastroenterology ,Serology ,Irritable Bowel Syndrome ,Diet, Gluten-Free ,Young Adult ,Asian People ,Internal medicine ,HLA-DQ Antigens ,medicine ,Prevalence ,Humans ,Young adult ,Irritable bowel syndrome ,Aged ,biology ,business.industry ,Haplotype ,General Medicine ,Middle Aged ,medicine.disease ,Diarrhea ,Celiac Disease ,Immunology ,biology.protein ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Gluten free ,Female ,Antibody ,medicine.symptom ,business ,Research Article - Abstract
Supplemental Digital Content is available in the text, Celiac disease (CD) is common in Caucasians, but thought to be rare in Asians. Our aim was to determine the prevalence of CD in Chinese patients with chronic diarrhea predominant irritable bowel syndrome (IBS-D). From July 2010 to August 2012, 395 adult patients with IBS-D and 363 age and sex-matched healthy controls were recruited in Zhongnan Hospital of Wuhan University and Xiaogan Central Hospital in Hubei province, central China. Patients with IBS-D were diagnosed according to the Rome III criteria. Serum Immunoglobulin (IgA/IgG) anti-human tissue transglutaminase (anti-htTG)-deamidated gliadin peptide (DGP) antibodies were measured in a single ELISA (QUANTA Lite h-tTG/DGP Screen). Upper endoscopy with duodenal biopsies and HLA-DQA1 and HLA-DQB1 genotyping were performed in seropositive subjects and a gluten-free diet was prescribed. Seven IBS-D patients (7/395, 1.77%) and 2 healthy controls (2/363, 0.55%), were positive for anti-htTG/DGP antibodies. Of these 9 cases, 1 was lost to follow-up, 3 were suspected to have CD and 5 were eventually diagnosed as CD with intestinal histological lesions classified as Marsh Type II in 2 and Type III in 3. Of these 5 diagnosed CD patients, 4 (4/395, 1.01%) were from the IBS-D group and 1 (1/363, 0.28%) from the healthy control had asymptomatic CD. Two Type III CD patients with relatively high titers in the serologic assay were homozygous and heterozygous for haplotype HLA-DQA1∗03-DQB1∗03:03 (HLA-DQ9.3), respectively. In the present study, CD was present in 1.01% of patients with IBS-D and in 0.28% of the control group. We like to suggest that the haplotype HLA-DQA1∗03-DQB1∗03:03 (HLA-DQ9.3), which is common in Chinese, is a new susceptibility factor for CD in China. Larger screening and genetic studies are needed in the Chinese population of different regions.
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- 2015
14. Genetic Variation in Myosin IXB Is Associated With Ulcerative Colitis
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Christopher G. Mathew, Mark J. Daly, Cisca Wijmenga, R. K. Linskens, Christine R. Curley, Alastair Forbes, Alain Bitton, Anna Latiano, J. Bart A. Crusius, Alienke J. Monsuur, John D. Rioux, David P. Strachan, Adriaan A. van Bodegraven, David A. van Heel, Natalie J. Prescott, Raymond J. Playford, Mark S. Silverberg, A. Hilary Steinhart, Jeremy D. Sanderson, Clive M. Onnie, Sheila A. Fisher, Karen A. Hunt, and Vito Annese
- Subjects
Adult ,Male ,Adolescent ,Genotype ,Single-nucleotide polymorphism ,Disease ,Myosins ,Biology ,Polymorphism, Single Nucleotide ,Inflammatory bowel disease ,White People ,Cohort Studies ,Genetic variation ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Child ,Aged ,Aged, 80 and over ,Intestinal permeability ,Hepatology ,Haplotype ,Gastroenterology ,Genetic Variation ,Middle Aged ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Case-Control Studies ,Immunology ,Colitis, Ulcerative ,Female - Abstract
Background & Aims: Common germline genetic variation in the 3′ region of myosin IXB ( MYO9B ) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. Methods: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3′ region of MYO9B . These included the strongest celiac disease–associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. Results: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 × 10 -6 ; odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. Conclusions: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases.
- Published
- 2006
15. TNF-857 polymorphism in Israeli Jewish patients with inflammatory bowel disease
- Author
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Herma Fidder, Simon Bar-Meir, Yehuda Chowers, Benjamin Avidan, J. Bart A. Crusius, Roel Heijmans, and A. Salvador Peña
- Subjects
Adult ,Genotype ,medicine.medical_treatment ,Immunology ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Inflammatory bowel disease ,Pathogenesis ,Crohn Disease ,Gene Frequency ,Genetics ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Israel ,Promoter Regions, Genetic ,Molecular Biology ,Allele frequency ,Alleles ,Genetics (clinical) ,Tumor Necrosis Factor-alpha ,business.industry ,General Medicine ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Phenotype ,Cytokine ,Jews ,Colitis, Ulcerative ,business - Abstract
Tumour necrosis factor (TNF)-alpha is an important pro-inflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The promoter TNF-857 C-->T single nucleotide polymorphism (SNP) is functional through the binding to the transcription factor octamer transcription factor-1 (OCT-1). In order to investigate the frequency of this SNP in Israeli Jewish IBD patients, we analysed a cohort of well-characterized patients, 153 with Crohn's disease (CD) and 78 with ulcerative colitis (UC) and 188 healthy controls individually matched for age, sex and ethnicity. Forty-one per cent of the patients were of Ashkenazi and 48% were of non-Ashkenazi background. The remaining 11% were of mixed Ashkenazi-non-Ashkenazi background. Patients and controls were genotyped for the TNF-857 SNP by Taqman technology. Stratification for the CARD15 Arg702Trp, Gly908Arg and Leu1007fsinsC mutations took place in 136 CD patients. Carrier frequency of TNF-857T between CD and controls (36% vs. 40%; P = 0.556; OR: 1.18, 95% CI 0.74-1.88), or between UC and controls (41% vs. 37%; P = 0.743; OR: 0.85, 95% CI 0.45-1.62) did not differ significantly. Neither did stratifying for the presence of at least one of the common CARD15 mutations result in a significant difference between CD and controls. No associations were found between TNF-857T and CD phenotype as defined by the Vienna classification, perianal disease or extra-intestinal disease irrespective of CARD15 carrier status. In conclusion, it appears that TNF-857 SNP does not contribute to susceptibility of IBD, neither does it define the phenotype of CD in Israeli Jewish IBD patients.
- Published
- 2006
16. Human Leukocyte Antigen–DQ2 Homozygosity and the Development of Refractory Celiac Disease and Enteropathy-Associated T-Cell Lymphoma
- Author
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Abdulbaqi Al–toma, J. Bart A. Crusius, Jos W. R. Meijer, A. Salvador Peña, Marije S. Goerres, and Chris J. J. Mulder
- Subjects
Adult ,Male ,Receptors, Antigen, T-Cell ,Disease ,Human leukocyte antigen ,Lymphoma, T-Cell ,Refractory ,Antigens, CD ,HLA-DQ Antigens ,medicine ,Humans ,Genetic Predisposition to Disease ,Enteropathy ,Aged ,Aged, 80 and over ,Hepatology ,business.industry ,Homozygote ,T-cell receptor ,Gastroenterology ,nutritional and metabolic diseases ,Odds ratio ,Middle Aged ,medicine.disease ,Celiac Disease ,Case-Control Studies ,Immunology ,Enteropathy-associated T-cell lymphoma ,Intraepithelial lymphocyte ,Female ,business - Abstract
Background & Aims: Celiac disease (CD) is a common gluten-sensitive enteropathy associated with human leukocyte antigen (HLA)-DQ2 and HLA-DQ8. The aim of this study was to determine if a particular HLA-DQ subtype predisposes to complications such as refractory CD with (RCD II) or without aberrant T cells (RCD I), and enteropathy-associated T-cell lymphomas (EATL). Methods: Molecular HLA-DQ typing was performed on 43 RCD I, 43 RCD II, and 30 EATL patients, and compared with age-matched groups of 121 patients with histologically defined uncomplicated CD and 183 healthy controls. All individuals were Dutch Caucasians and were at least 21 years of age. Results: HLA-DQ2 was present in 79% of RCD I, 97.7% of RCD II, and 96.6% of EATL patients. The differences were significant when compared with 28.9% in controls but not with 91.7% in uncomplicated CD. Homozygosity for HLA-DQ2 was observed in 25.5% of RCD I, 44.1% of RCD II, and 53.3% of EATL patients vs 20.7% of uncomplicated CD patients and 2.1% of controls. HLA-DQ8 was present in 10.7% of CD, 16.2% of RCD I, 9.3% of RCD II, and 6.6% of EATL patients vs 20.2% of controls. Conclusions: Homozygosity for HLA-DQ2 is associated with RCD II and EATL. Early identification of HLA-DQ2 homozygous CD patients may help to recognize CD patients at risk for developing these severe complications.
- Published
- 2006
17. The Familial Mediterranean Fever (MEVF) Gene as a Modifier of Crohn's Disease
- Author
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Zvi Ackerman, Herma Fidder, Yehuda Chowers, Avi Livneh, Benjamin Avidan, Yael Shinhar, J. Bart A. Crusius, Rivka Dresner Pollak, and Simon Bar-Meir
- Subjects
Adult ,Male ,Heterozygote ,Systemic disease ,Genotype ,Familial Mediterranean fever ,Disease ,Crohn Disease ,NOD2 ,medicine ,Humans ,Genetic Predisposition to Disease ,Autoimmune disease ,Crohn's disease ,Hepatology ,business.industry ,Gastroenterology ,Proteins ,Pyrin ,medicine.disease ,MEFV ,Familial Mediterranean Fever ,Cytoskeletal Proteins ,Phenotype ,Jews ,Mutation ,Immunology ,Female ,Age of onset ,business - Abstract
OBJECTIVES: Crohn’s disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV )h ave been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation. AIMS: To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation. METHODS: Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi‐non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q .F ive patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens. RESULTS: The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3‐10.5, p = 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65% vs 32%, OR 3.9, 95% CI = 1.3‐11.5, p = 0.015). No differences were observed in disease location and disease severity. CONCLUSIONS: MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD. (Am J Gastroenterol 2005;100:338‐343)
- Published
- 2005
18. A candidate gene approach of immune mediators effecting the susceptibility to and severity of upper gastrointestinal tract diseases in relation to Helicobacter pylori and Epstein-Barr virus infections
- Author
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A. Salvador Peña, Servaas A. Morré, Elly C. Klinkenberg-Knol, J. Bart A. Crusius, Sander Ouburg, Chris J. J. Mulder, and VU University medical center
- Subjects
Lymphotoxin alpha ,Candidate gene ,Epstein-Barr Virus Infections ,Gastrointestinal Diseases ,Single-nucleotide polymorphism ,Disease ,Helicobacter Infections ,Pathogenesis ,Immune system ,Immunogenetics ,Medicine ,Humans ,Genetic Predisposition to Disease ,Epstein–Barr virus infection ,Polymorphism, Genetic ,Hepatology ,biology ,Helicobacter pylori ,business.industry ,Gastroenterology ,biology.organism_classification ,medicine.disease ,Immunology ,Cytokines ,business ,Interleukin-1 - Abstract
This review focuses on immunogenetic aspects of diseases of the upper gastrointestinal tract in which infectious agents may play a role in the aetiopathogenesis, such as Helicobacter pylori, Epstein-Barr virus (EBV) and HIV. Gastric adenocarcinoma is a common cancer all around the world, with declining incidences in Europe and high incidences in Asia and central and south America. Together with gastric atrophy and peptic ulcer disease, gastric adenocarcinoma belongs to the commonest upper gastrointestinal tract diseases. These diseases are multifactorial and factors such as smoking and dietary habits contribute to the pathogenesis. More recently, scientists have turned their eyes on the host. Functional polymorphisms in the genes regulating the host immune system may contribute to the susceptibility to and progression of disease. In multifactorial and polygenetic diseases, candidate gene studies of single nucleotide polymorphisms (SNPs) detect small to moderate relative risks. Unfortunately, only a few functional SNPs have been identified. The candidate gene approach can be seen as a useful first step in exploring causal pathways between genetic determinants and complex diseases such as those mentioned above. To date, little is known about the immunogenetics of upper gastrointestinal tract diseases. We review the literature on H. pylori, EBV and gene polymorphisms that affect key immune mediators influencing the pathogenesis of the inflammatory response, such as the genes that code for the IL-1 family, TNF-alpha, lymphotoxin alpha, and IL-10. IL-1, IL-10, lymphotoxin alpha and TNF-alpha polymorphisms increase the risk of upper gastrointestinal pathogenesis in H. pylori-infected patients, whereas IL-1 and TNF-alpha polymorphisms confer risk in EBV-infected patients.
- Published
- 2005
19. Gender-Related Association Between the TGFBI+869 Polymorphism and Multiple Sclerosis
- Author
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Chris H. Polman, Bernard M. J. Uitdehaag, Hans M. Schrijver, M. Asunción García-González, J. Bart A. Crusius, A. Salvador Peña, and Frederik Barkhof
- Subjects
Genetics ,Multiple sclerosis ,Immunology ,Haplotype ,Single-nucleotide polymorphism ,Cell Biology ,Biology ,medicine.disease ,Gender related ,Virology ,Genotype ,medicine ,In patient ,Allele ,Gene - Abstract
Our objective was to investigate whether polymorphisms and haplotypes in the TGFB1 gene are associated with susceptibility or disease characteristics of multiple sclerosis (MS). In 247 MS patients and 194 controls, single nucleotide polymorphisms (SNPs) at position +869 (Leu10Pro) and position +915 (Arg25Pro) in the signaling sequence of the TGFB1 gene were determined, and the distribution of alleles, genotypes, and haplotypes was related to clinical data. In addition, magnetic resonance imaging (MRI) data were studied in a subgroup of patients (n = 96). The allele distribution of the two polymorphisms studied was in Hardy- Weinberg equilibrium in patients and in controls. No association was found with any of the three haplotypes found in the Dutch population, denoted as haplotype 1 (TGFB1+869T–TGFB1+915G), haplotype 2 (TGFB1+869C–TGFB1+915G), and haplotype 3 (TGFB1+869C–TGFB1+915C). However, the TGFB1+869 genotype CC was significantly more frequent in patients (p = 0.031, χ2 test). The highest frequency ...
- Published
- 2004
20. Gender-Related Association Between the TGFB1+869 Polymorphism and Multiple Sclerosis
- Author
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Hans M. Schrijver, J. Bart A. Crusius, M. Asunçion García-González, Chris H. Polman, A. Salvador Peña, Frederik Barkhof, and Bernard M.J. Uitdehaag
- Subjects
Virology ,Immunology ,Cell Biology - Published
- 2004
21. Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1β and IL-1ra production in multiple sclerosis
- Author
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Jaco van As, Christien D. Dijkstra, J. Bart A. Crusius, Hans M. Schrijver, and Bernard M. J. Uitdehaag
- Subjects
Adult ,Male ,Heterozygote ,Sialoglycoproteins ,Immunology ,Gene Dosage ,Biology ,Severity of Illness Index ,Gene dosage ,Multiple sclerosis ,Multiple Sclerosis, Relapsing-Remitting ,medicine ,Genetics ,lcsh:Pathology ,Humans ,Allele ,Alleles ,Whole blood ,Polymorphism, Genetic ,Interleukin ,Heterozygote advantage ,Cell Biology ,Middle Aged ,Multiple Sclerosis, Chronic Progressive ,medicine.disease ,Pathophysiology ,Interleukin-1 receptor antagonist ,Cytokines ,Interleukin 1 Receptor Antagonist Protein ,Interleukin 1 receptor antagonist ,Female ,Research Article ,Interleukin-1 ,lcsh:RB1-214 - Abstract
Background:Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1Band IL-1 receptor antagonist(IL−1RN)genes (i.e.IL−1RNallele2+/IL−1B+3959allele 2−) with disease severity in MS. Extending this observation, we investigated whether IL-1β and IL-1ra production differed depending on carriership of this gene combination.Methods:Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood,in vitroIL-1β and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide.Results:Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous forIL−1RNallele 2. In patients, Il-1ra production was higher and IL-1β production lower compared with controls. In primary progressive patients, the IL-1β /IL-1ra ratio was significantly lower than in relapsing-remitting patients.Conclusion:Our results suggest higher in vitro IL-1ra production in carriers ofIL−1RNallele 2, with an indication of an allelic dose-effect relationship.
- Published
- 2003
22. Polymorphisms in the tumor necrosis factor and lymphotoxin-α gene region and preeclampsia
- Author
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J. Bart A. Crusius, Augusta M. A. Lachmeijer, Reynir Arngrímsson, G.A. Dekker, Gerard Pals, and Leo P. ten Kate
- Subjects
Lymphotoxin alpha ,HELLP Syndrome ,medicine.medical_specialty ,HELLP syndrome ,Pilot Projects ,Preeclampsia ,Pre-Eclampsia ,Pregnancy ,Internal medicine ,medicine ,Humans ,Eclampsia ,Allele ,Lymphotoxin-alpha ,Polymorphism, Genetic ,Tumor Necrosis Factor-alpha ,business.industry ,Haplotype ,Case-control study ,Obstetrics and Gynecology ,Odds ratio ,medicine.disease ,Endocrinology ,Haplotypes ,Case-Control Studies ,Female ,Lod Score ,business ,Microsatellite Repeats - Abstract
OBJECTIVE: To investigate potential association or linkage among nine polymorphisms in the genes encoding tumor necrosis factor (TNF) α or lymphotoxin (LT) α and preeclampsia. METHODS: Four di-allelic polymorphisms and five microsatellite markers in the genes encoding TNF-α (TNF) and LTα (LTA) and their haplotypes were studied in 150 Dutch families. These families contained sib-pairs of women affected with preeclampsia; eclampsia; the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (strict criteria); or pregnancy-induced hypertension (mild criteria). Frequencies were compared with 98 healthy controls. Nonparametric affected sib-pair analyses for allele sharing among siblings were carried out for all nine markers. Each sibship was composed of an affected index woman and one or more affected sisters. RESULTS: Although we found a striking association with the TNF-I haplotype in 30 index women with (pre-)eclampsia or HELLP syndrome compared with controls (odds ratio [OR] 3.8; 95% confidence interval [CI] 1.6, 8.9), this association was not found in their 30 sisters meeting similar disease criteria. Analyses in all 150 families showed a similar TNF-I association in 122 index women meeting the strict criteria compared with controls (OR 1.9; 95% CI 1.1, 3.3), but, again, not in their 91 sisters meeting similar disease criteria. This association was stronger in a subgroup of 75 index women with preeclampsia only (OR 2.3; 95% CI 1.2, 4.2). No excess allele sharing for any marker was seen between the siblings. CONCLUSION: The nine polymorphisms studied in the TNF-LTA region did not show evidence for association or linkage with familial preeclampsia.
- Published
- 2001
23. Polymorphisms in the Tumor Necrosis Factor and Lymphotoxin-α Gene Region and Preeclampsia
- Author
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Augusta M. A. Lachmeijer, J. Bart A. Crusius, Gerard Pals, Guustaaf A. Dekker, Reynir Arngrímsson, and Leo P. ten Kate
- Subjects
Obstetrics and Gynecology - Published
- 2001
24. Gluten Challenge in Borderline Gluten-Sensitive Enteropathy
- Author
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Chris J. J. Mulder, J Bart A Crusius, Peter J. Wahab, and Jos W. R. Meijer
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Malabsorption ,Adolescent ,Glutens ,Normal diet ,Biopsy ,digestive system ,Gastroenterology ,Antibodies ,Gliadin ,Lesion ,Intestinal mucosa ,Internal medicine ,Intestine, Small ,medicine ,Humans ,Enteropathy ,Intestinal Mucosa ,Villous atrophy ,Aged ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Hepatology ,biology ,business.industry ,Muscles ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Gluten ,digestive system diseases ,Celiac Disease ,chemistry ,biology.protein ,Female ,medicine.symptom ,business - Abstract
OBJECTIVES: In patients with signs and symptoms of malabsorption, suggestive of gluten-sensitive enteropathy, small intestinal biopsies sometimes only reveal infiltration of lymphocytes into the mucosal epithelium. This infiltrative lesion (Marsh I) is not a definite proof for gluten-sensitive enteropathy. However, in the present study, we aimed to show that a subgroup of these patients could ultimately be identified as being gluten sensitive. METHODS: A total of 38 patients with a Marsh I lesion were subjected to a gluten challenge comprising 30 g of gluten added daily to a normal gluten-containing diet for 8 wk. Before and after the challenge, small intestinal biopsies were taken, and symptoms and signs of malabsorption were scored. RESULTS: In 12 patients we demonstrated a significant change in mucosal histopathology, i.e., subtotal villous atrophy (Marsh IIIB, n = 1), partial villous atrophy (Marsh 3A, n = 6) or infiltrative-crypthyperplastic lesions (Marsh II, n = 5). In the other 26 patients, the small intestinal mucosa remained unchanged. After initiation of a gluten-free diet, follow-up small intestinal biopsies in 12 patients who initially had progressive mucosal pathology after gluten challenge showed normalization of mucosal pathology in seven cases, regression to a Marsh I lesion in four, and to a Marsh II lesion in one. Symptom relief was seen in all 12 patients. Ten of 26 patients without histological response to the gluten challenge were motivated to adhere to a gluten-free diet. Follow-up biopsies revealed unchanged Marsh I lesions in eight patients and normalization (Marsh 0) in two patients. Three patients had follow-up biopsies while on a normal diet. All had unchanged Marsh I lesions. CONCLUSIONS: In the present study we demonstrated that a gluten challenge might be useful in identifying patients as being sensitive to gluten if initial small intestinal biopsies reveal only minor abnormalities.
- Published
- 2001
25. TNF-α promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients
- Author
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Chris H. Polman, Ferdinand C. Breedveld, Jan A.M. Langermans, Bob W. van Oosten, Rudi G. J. Westendorp, Tom W J Huizinga, Vivian Keijsers, Lieve Dams, Asunción Garcı́a-Gonzalez, Cornelis L. Verweij, Luc van de Gaer, A. Salvador Peña, Eduard L. E. M. Bollen, Brigitta M. N. Brinkman, J. Bart A. Crusius, Pathology, Medical Microbiology and Infection Prevention, Neurology, Amsterdam Neuroscience - Neuroinfection & -inflammation, and NCA - Neuroinflamation
- Subjects
medicine.medical_specialty ,Multiple Sclerosis ,Immunology ,Stimulation ,TNF production ,Polymorphism (computer science) ,Internal medicine ,Genotype ,Humans ,Immunology and Allergy ,Medicine ,Promoter Regions, Genetic ,Whole blood ,Polymorphism, Genetic ,Tumor Necrosis Factor-alpha ,business.industry ,Multiple sclerosis ,medicine.disease ,Endocrinology ,Neurology ,Tumor necrosis factor alpha ,Disease Susceptibility ,Neurology (clinical) ,Gene polymorphism ,business - Abstract
TNF-alpha production in whole blood cultures upon stimulation with LPS was determined in 179 individuals from 61 families in order to characterise the magnitude of inherited differences in TNF-alpha production. The three families characterised by highest TNF production showed 7.1 +/- 0.3 ng TNF/ml upon culture with 10 ng LPS and 10.2 +/- 0.2 ng TNF/ml upon culture with 1000 ng LPS. in contrast to the three families characterised by the lowest TNF production that showed a production of 1.6 +/- 0.1 ng TNF upon culture with 10 ng and 2.5 +/- 0.2 ng/ml upon culture with 1000 ng LPS/ml. This difference could not be attributed to the promoter polymorphisms -308 G to A. -238 G to A or -376 G to A, although the -238 GA donors produced 2.1 +/- 0.9 ng TNF upon culture with 10 ng endotoxin compared to 3.2 +/- 2.2 ng TNF for the -238 GG donors. In line with these results the frequency of the -238 GG genotype was increased in hospitalized MS patients in a nursing home (100% 238GG, n = 57) compared to MS patients in an outpatient's clinic (94% 238GG, n = 98) or Dutch controls (90% 238GG, n = 180). These results suggest that the -238 GG genotype is differently distributed in hospitalized MS patients in a nursing home.
- Published
- 1997
26. Genome-wide Association Study and Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis
- Author
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Henk-Jan Guchelaar, Leonid Padyukov, Eli A. Stahl, Sara Wedrén, J. Bart A. Crusius, Atsuo Taniguchi, Dorothee Diogo, Mart A F J van de Laar, Towfique Raj, Saedis Saevarsdottir, Soumya Raychaudhuri, Helena Canhão, Anne Barton, Tom W J Huizinga, Jing Cui, M M J Herenius, Fumihiko Matsuda, Kimme L. Hyrich, Gertjan Wolbink, Barbara E. Stranger, Maša Umiċeviċ Mirkov, Robert P. Kimberly, Koichiro Ohmura, René E. M. Toes, Lindsey A. Criswell, Larry W. Moreland, Peter K. Gregersen, Shigeki Momohara, Chikashi Terao, Niek de Vries, Ann W. Morgan, Johan Askling, Xavier Mariette, João Eurico Fonseca, Hisashi Yamanaka, Elizabeth W. Karlson, Corinne Miceli, Manik Kuchroo, S. Louis Bridges, Tsuneyo Mimori, Katsunori Ikari, John D. Isaacs, Yukinori Okada, Piet L. C. M. van Riel, Philip L. De Jager, Gosia Trynka, Michael E. Weinblatt, Marieke J H Coenen, Namrata Gupta, Anthony G. Wilson, Nancy A. Shadick, Marieke E. Doorenspleet, Robert M. Plenge, Cornelia F Allaart, Irene E. van der Horst-Bruinsma, Paul P. Tak, Rheumatology, Medical Microbiology and Infection Prevention, CCA - Innovative therapy, Clinical Immunology and Rheumatology, Graduate School, Landsteiner Laboratory, and AII - Amsterdam institute for Infection and Immunity
- Subjects
Male ,Cancer Research ,Gene Expression ,Genome-wide association study ,Biomarkers, Pharmacological ,Receptors, Tumor Necrosis Factor ,Etanercept ,Arthritis, Rheumatoid ,0302 clinical medicine ,skin and connective tissue diseases ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Genetics (clinical) ,Regulation of gene expression ,0303 health sciences ,Middle Aged ,3. Good health ,Antirheumatic Agents ,Rheumatoid arthritis ,Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2] ,Female ,Research Article ,medicine.drug ,Adult ,musculoskeletal diseases ,medicine.medical_specialty ,lcsh:QH426-470 ,Biology ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Asian People ,Antigens, CD ,Signaling Lymphocytic Activation Molecule Family ,Molecular genetics ,Genome-Wide Association Studies ,Genetics ,Adalimumab ,medicine ,Humans ,SNP ,Molecular Biology ,Genomic disorders and inherited multi-system disorders Molecular epidemiology [IGMD 3] ,Alleles ,Ecology, Evolution, Behavior and Systematics ,Aged ,030304 developmental biology ,030203 arthritis & rheumatology ,Tumor Necrosis Factor-alpha ,medicine.disease ,Infliximab ,lcsh:Genetics ,Gene Expression Regulation ,Immunoglobulin G ,Immunology ,Genome-Wide Association Study - Abstract
Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10−8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10−11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry., Author Summary There are no genetic predictors of response to one of the most widely used classes of drugs in the treatment of rheumatoid arthritis—biological modifiers of the inflammatory cytokine tumor necrosis factor-alpha (or anti-TNF therapy). To identify genetic predictors, we performed the largest genome-wide association study (GWAS) to date as part of an international collaboration. In our study, which included 2,706 RA patients treated with one of three anti-TNF drugs, the most significant finding was restricted to RA patients treated with etanercept (P = 8×10−8), a drug that acts as a soluble receptor to bind circulating cytokine and prevents TNF from binding to its cell surface receptor. The associated variant influences expression of a nearby immune-related gene, CD84, whose expression is correlated with disease activity in RA patients. Together, our data support a model in which genomic factors related to CD84 expression serve as a predictor of disease activity and response to etanercept therapy among RA patients of European ancestry, but not anti-TNF therapies that act through different biological mechanisms or potentially in RA patients of other genetic ancestries.
- Published
- 2013
27. Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis
- Author
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Murray L. Barclay, Rinse K. Weersma, Javier Martín, Lina-Marcela Diaz-Gallo, J. Bart A. Crusius, Rebecca L. Roberts, Tony R. Merriman, Elena Urcelay, Carlos Taxonera, Laura Espino-Paisán, Miguel A. López-Nevot, Cisca Wijmenga, Behrooz Z. Alizadeh, María Gómez-García, Ignacio Cueto, Suzanne van Sommeren, Karin Fransen, Antonio Nieto, Guillermo Alcain, Nunzio Bottini, Luis Rodrigo, Juan Luis Mendoza, Cyriel Y. Ponsioen, Richard B. Gearry, Carlos Cardeña, Adriaan A. van Bodegraven, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Gastroenterology and hepatology, CCA - Immuno-pathogenesis, and Pathology
- Subjects
Pathology ,endocrine system diseases ,lcsh:Medicine ,Genome-wide association study ,protein tyrosine phosphatase ,medicine.disease_cause ,Inflammatory bowel disease ,Gastroenterology ,Crohn's disease (CD) ,Autoimmunity ,Exon ,Crohn Disease ,immune system diseases ,Risk Factors ,MULTIPLE ,Odds Ratio ,Immunology and Allergy ,skin and connective tissue diseases ,POPULATION ,Medicine(all) ,education.field_of_study ,Crohn's disease ,LYMPHOID TYROSINE PHOSPHATASE ,General Medicine ,Prognosis ,Ulcerative colitis ,inflammatory bowel disease (IBD) ,nonreceptor type 22 (PTPN22) gene ,musculoskeletal diseases ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,Genotype ,Population ,AUTOIMMUNE-DISEASES ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,White People ,PTPN22 ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Risk factor ,education ,Genotyping ,7 COMMON DISEASES ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,lcsh:R ,Case-control study ,Protein Tyrosine Phosphatase, Non-Receptor Type 22 ,Odds ratio ,medicine.disease ,RISK LOCI ,GENE ,Ptpn22 gene ,eye diseases ,ulcerative colitis (UC) ,Minor allele frequency ,Spain ,Case-Control Studies ,Immunology ,Poster Presentation ,Colitis, Ulcerative ,business ,INFLAMMATORY-BOWEL-DISEASE ,New Zealand - Abstract
2 páginas.-- Póster presentado al 5º European Workshop on Immune-Mediated Inflammatory Diseases celebrado en Sitges (Barcelona) dxel 1 al 3 de Diciembre de 2010.-- et al., The PTPN22 gene is an important risk factor for human autoimmunity. Two PTPN22 missense-SNPs, both with functional influence, the R620W (1858C>T, rs2476601) in exon 14 and the R263Q (788G>A, rs33996649) in exon 10 have been associated with autoimmune diseases [1-4].
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- 2010
28. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci
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Robert M. Plenge, Elisabeth Brouwer, Cisca Wijmenga, Christopher I. Amos, Anthony G. Wilson, Noël P. Burtt, Stephen Eyre, Paul P. Tak, Pille Harrison, Daniel L. Kastner, Robert Chen, Gang Xie, Gertjan Wolbink, Bo Ding, Niek de Vries, B. Paul Wordsworth, Paul I.W. de Bakker, David M. Reid, Xiangdong Liu, Mark Seielstad, Tom W J Huizinga, Lynne J. Hocking, Peter K. Gregersen, Leonid Padyukov, Jing Cui, Annette Lee, Sophia Steer, J. Bart A. Crusius, C. Ellen van der Schoot, Yonghong Li, Philip L. De Jager, Michael F. Seldin, Kristin G. Ardlie, Anne Barton, Marieke J H Coenen, Annette H M van der Helm-van Mil, Nancy A. Shadick, Ann W. Morgan, Fina A S Kurreeman, Katherine A. Siminovitch, Elaine F. Remmers, Timothy R D J Radstake, René E. M. Toes, Anne Hinks, Jane Worthington, Karen H. Costenbader, Joseph J. Catanese, Elizabeth W. Karlson, Alexandra Zhernakova, Edward Flynn, Xiayi Ke, Brian Thomson, Soumya Raychaudhuri, Jonathan S. Coblyn, Lars Alfredsson, Marcel D. Posthumus, John Bowes, Irene E. van der Horst-Bruinsma, Ann B. Begovich, Wendy Thomson, Paul Martin, Candace Guiducci, Piet L. C. M. van Riel, Paul Emery, Michael E. Weinblatt, Lars Klareskog, Lindsey A. Criswell, Eli A. Stahl, Rheumatology, CCA - Disease profiling, Pathology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, Landsteiner Laboratory, and Clinical Haematology
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SUSCEPTIBILITY LOCI ,Arthritis ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,VARIANTS ,Polymorphism, Single Nucleotide ,Auto-immunity, transplantation and immunotherapy [N4i 4] ,Article ,REGION ,Arthritis, Rheumatoid ,Genomic disorders and inherited multi-system disorders [IGMD 3] ,Molecular epidemiology [NCEBP 1] ,systemic-lupus-erythematosus susceptibility loci celiac-disease variants gene common region polymorphisms confirmation replication ,Risk Factors ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,Health care ethics [NCEBP 5] ,COMMON ,POLYMORPHISMS ,Autoantibodies ,Autoantibody ,CELIAC-DISEASE ,medicine.disease ,GENE ,CONFIRMATION ,Genetic Loci ,Evaluation of complex medical interventions [NCEBP 2] ,Rheumatoid arthritis ,PADI4 ,Immunology ,REPLICATION ,IRF5 ,Genome-Wide Association Study - Abstract
Contains fulltext : 88498.pdf (Publisher’s version ) (Closed access) To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles. 01 juni 2010
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- 2010
29. Analysis of multiple candidate genes in association with phenotypes of multiple sclerosis
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J. Bart A. Crusius, Bernard M. J. Uitdehaag, Mark A. van de Wiel, Joep Killestein, Chris H. Polman, Diego Tejedor, A. Salvador Peña, David Arteta, Antonio Martinez, Madeleine H. Sombekke, Neurology, Epidemiology and Data Science, Pathology, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Stochastics, Mathematics, and Neuroscience Campus Amsterdam - Multiple Sclerosis and Other Neuroinflammatory Diseases
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Candidate gene ,Multiple Sclerosis ,Genotype ,Single-nucleotide polymorphism ,Disease ,macromolecular substances ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Central nervous system disease ,Degenerative disease ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Gene ,Genetic Association Studies ,Expanded Disability Status Scale ,Chi-Square Distribution ,business.industry ,Multiple sclerosis ,Middle Aged ,medicine.disease ,Phenotype ,Neurology ,nervous system ,Area Under Curve ,Immunology ,Female ,Neurology (clinical) ,business - Abstract
Multiple sclerosis is a heterogeneous neurological disease with varying degrees of severity. The common hypothesis is that susceptibility to multiple sclerosis and its phenotype are caused by a combination of environmental and genetic factors. The genetic part exerts its effect through several genes, each having modest effects. We evaluated whether disease severity could be predicted by a model based on clinical data and data from a DNA chip. The DNA chip was designed containing several single nucleotide polymorphisms in 44 genes, previously described to be associated with multiple sclerosis. A total of 605 patients with multiple sclerosis were included in this analysis, using gender, onset type and age at onset as clinical covariates. We correlated 80 single nucleotide polymorphisms to the degree of disease severity using the following three outcome measures: linear Multiple Sclerosis Severity Score, dichotomous Multiple Sclerosis Severity Score (using a cut-off point of 2.5) and time to reach Expanded Disability Status Scale score 6. Sixty-nine single nucleotide polymorphisms were included in the analysis. No individual single nucleotide polymorphism showed a significant association; however, a combination of single nucleotide polymorphisms significantly improved the prediction of disease severity in addition to the clinical variables. In all three models the Interleukin 2 gene was included, confirming a previously reported modest effect on disease severity. The highest power was obtained using the dichotomized Multiple Sclerosis Severity Score as outcome. Several single nucleotide polymorphisms showed their added predictive value over the clinical data in the predictive models. These results support our hypothesis that disease severity is determined by clinical variables and genetic influences (through several genes with small effects) in concert.
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- 2010
30. New insights in understanding the pathogenesis of spondyloarthropathies
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Irene E. van der Horst-Bruinsma, J. Bart A. Crusius, Rheumatology, CCA - Immuno-pathogenesis, and Pathology
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Adult ,Male ,Immunology ,Gene Expression ,Nerve Tissue Proteins ,Inflammation ,Bone remodeling ,Rheumatology ,medicine ,Humans ,Immunology and Allergy ,Osteonectin ,Spondylarthropathies ,Oligonucleotide Array Sequence Analysis ,Ankylosing spondylitis ,Innate immune system ,business.industry ,Ossification ,Gene Expression Profiling ,Membrane Proteins ,Blood Proteins ,Middle Aged ,medicine.disease ,Gene expression profiling ,Editorial ,Female ,medicine.symptom ,business ,Uveitis ,Research Article - Abstract
Introduction Axial spondyloarthropathy (SpA) is a group of inflammatory diseases, with ankylosing spondylitis as the prototype. SpA affects the axial skeleton, entheses, joints and, at times, the eyes. This study tested the hypothesis that SpA is characterized by a distinct pattern of gene expression in peripheral blood of affected individuals compared with healthy controls. Methods High-density, human GeneChip® probe arrays were used to profile mRNA of peripheral blood cells from 18 subjects with SpA and 25 normal individuals. Samples were processed as two separate sets at different times (11 SpA + 12 control subjects in primary set (Set 1); 7 SpA+ 13 control subjects in the validation set (Set 2)). Blood samples were taken at a time when patients were not receiving systemic immunomodulatory therapy. Differential expression was defined as a 1.5-fold change with a q value < 5%. Gene ontology and pathway information were also studied. Results Signals from 134 probe sets (representing 95 known and 12 unknown gene transcripts) were consistently different from controls in both Sets 1 and 2. Included among these were transcripts for a group of 20 genes, such as interleukin-1 (IL-1) receptors 1 and 2, Nod-like receptor family, pyrin domain containing 2 (NLRP2), secretory leukocyte peptidase inhibitor (SLPI), secreted protein acidic and rich in cysteine (SPARC), and triggering receptor expressed on myeloid cells 1 (TREM-1) that are clearly related to the immune or inflammatory response and a group of 4 transcripts that have a strong role in bone remodeling. Conclusions Our observations are the first to implicate SPARC, SLPI, and NLRP2, a component of the innate immune system, in the pathogenesis of SpA. Our results also indicate a possible role for IL-1 and its receptors in SpA. In accord with the bone pathology component of SpA, we also found that expression levels of transcripts reflecting bone remodeling factors are also distinguishable in peripheral blood from patients with SpA versus controls. These results confirm some previously identified biomarkers implicated in the pathogenesis of SpA and also point to novel mediators in this disease.
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- 2010
31. PTPRCrheumatoid arthritis risk allele is also associated with response to anti-TNF therapy
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Johan Askling, Peter K. Gregersen, Joanne Nititham, Soumya Raychaudhuri, Candace Guiducci, Lars Klareskog, Timothy W. Behrens, Lindsey A. Criswell, Ann W. Morgan, Kimme L. Hyrich, Niek de Vries, Tom W J Huizinga, John D. Isaacs, Robert M. Plenge, Laura B. Hughes, Saedis Saevarsdottir, Michael E. Weinblatt, Nancy A. Shadick, Annette H M van der Helm-van Mil, Paul P. Tak, Franak Batliwalla, Bo Ding, Irene E. van der Horst-Bruinsma, Michael F. Seldin, Anne Barton, Leonid Padyukov, Anthony G. Wilson, Jane Worthington, Gertjan Wolbink, René E. M. Toes, S. Louis Bridges, Brian Thomson, Elizabeth W. Karlson, M M J Herenius, Lars Alfredsson, Cornelia F Allaart, Larry W. Moreland, Sara Wedrén, J. Bart A. Crusius, Marlena Kern, and Jing Cui
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Oncology ,medicine.medical_specialty ,PTPRC Gene ,Immunology ,Arthritis ,PTPRC ,Etanercept ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,030304 developmental biology ,030203 arthritis & rheumatology ,0303 health sciences ,biology ,business.industry ,Odds ratio ,medicine.disease ,Infliximab ,3. Good health ,Rheumatoid arthritis ,biology.protein ,business ,medicine.drug - Abstract
Objective Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (▵DAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ▵DAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections.
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- 2010
32. Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti-Tumor Necrosis Factor alpha Therapy
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Jing, Cui, Saedis, Saevarsdottir, Brian, Thomson, Leonid, Padyukov, Annette H M, van der Helm-van Mil, Joanne, Nititham, Laura B, Hughes, Niek, de Vries, Soumya, Raychaudhuri, Lars, Alfredsson, Johan, Askling, Sara, Wedrén, Bo, Ding, Candace, Guiducci, Gert Jan, Wolbink, J Bart A, Crusius, Irene E, van der Horst-Bruinsma, Marieke, Herenius, Michael E, Weinblatt, Nancy A, Shadick, Jane, Worthington, Franak, Batliwalla, Marlena, Kern, Ann W, Morgan, Anthony G, Wilson, John D, Isaacs, Kimme, Hyrich, Michael F, Seldin, Larry W, Moreland, Timothy W, Behrens, Cornelia F, Allaart, Lindsey A, Criswell, Tom W J, Huizinga, Paul P, Tak, S Louis, Bridges, Rene E M, Toes, Anne, Barton, Lars, Klareskog, Peter K, Gregersen, Elizabeth W, Karlson, Robert M, Plenge, Rheumatology, Pathology, CCA - Innovative therapy, AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, and Landsteiner Laboratory
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Male ,Tumor Necrosis Factor-alpha ,Health Status ,International Cooperation ,Antibodies, Monoclonal ,Middle Aged ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Article ,Arthritis, Rheumatoid ,Disability Evaluation ,Treatment Outcome ,Risk Factors ,Antirheumatic Agents ,Humans ,Leukocyte Common Antigens ,Female ,Genetic Predisposition to Disease - Abstract
OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (triangle upDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. RESULTS: Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the triangle upDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39-0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41-1.99). CONCLUSION: Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections
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- 2010
33. Genetic association analysis of the functional c.714T>G polymorphism and mucosal expression of dectin-1 in inflammatory bowel disease
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Mihai G. Netea, R. K. Linskens, Theo S. Plantinga, Leo A. B. Joosten, J. Bart A. Crusius, Eleonora A. M. Festen, Rinse K. Weersma, J. Han van Krieken, Dirk J. de Jong, Rinke Stienstra, Ad A. van Bodegraven, Hilbert S. de Vries, Gastroenterology and hepatology, Pathology, and Other Research
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Adult ,Male ,Health aging / healthy living [IGMD 5] ,Age-related aspects of cancer [ONCOL 2] ,Genetics and epigenetic pathways of disease [NCMLS 6] ,Colon ,medicine.medical_treatment ,Interleukin-1beta ,Immunology/Innate Immunity ,Nod2 Signaling Adaptor Protein ,lcsh:Medicine ,Nerve Tissue Proteins ,Single-nucleotide polymorphism ,Biology ,Inflammatory bowel disease ,Translational research [ONCOL 3] ,NOD2 ,Genotype ,medicine ,Humans ,Genetic Predisposition to Disease ,Lectins, C-Type ,Myeloid Cells ,lcsh:Science ,Genetics and Genomics/Genetics of Disease ,Inflammation ,Crohn's disease ,Polymorphism, Genetic ,Gastroenterology and Hepatology/Inflammatory Bowel Disease ,Multidisciplinary ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,Tumor Necrosis Factor-alpha ,lcsh:R ,Genetic Variation ,Membrane Proteins ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Pathogenesis and modulation of inflammation [N4i 1] ,Cytokine ,Case-Control Studies ,Immunology ,Codon, Terminator ,Female ,Tumor necrosis factor alpha ,lcsh:Q ,Infection and autoimmunity [NCMLS 1] ,Research Article - Abstract
Background: Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes b-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Upon activation, dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). An early stop codon polymorphism (c.714T.G) in DECTIN-1 results in a loss-of-function (p.Y238X) and impaired cytokine responses, including TNF-a, interleukin (IL)-1b and IL-17 upon in vitro stimulation with Candida albicans or b-glucan. The aim of the present study was to test the hypothesis that the DECTIN-1 c.714T.G (p.Y238X) polymorphism is associated with lower disease susceptibility or severity in IBD and to investigate the level of dectin-1 expression in inflamed and non-inflamed colon tissue of IBD patients. Methodology: Paraffin embedded tissue samples from non-inflamed and inflamed colon of IBD patients and from diverticulitis patients were immunohistochemically stained for dectin-1 and related to CD68 macrophage staining. Genomic DNA of IBD patients (778 patients with Crohn’s disease and 759 patients with ulcerative colitis) and healthy controls (n=772) was genotyped for the c.714T.G polymorphism and genotype-phenotype interactions were investigated. Principal Findings: Increased expression of dectin-1 was observed in actively inflamed colon tissue, as compared to noninflamed tissue of the same patients. Also an increase in dectin-1 expression was apparent in diverticulitis tissue. No statistically significant difference in DECTIN-1 c.714T.G allele frequencies was observed between IBD patients and healthy controls. Furthermore, no differences in clinical characteristics could be observed related to DECTIN-1 genotype, neither alone, nor stratified for NOD2 genotype. Conclusions: Our data demonstrate that dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in IBD. The DECTIN-1 c.714T.G polymorphism however, is not a major susceptibility factor for developing IBD. Citation: de Vries HS, Plantinga TS, van Krieken JH, Stienstra R, van Bodegraven AA, et al. (2009) Genetic Association Analysis of the Functional c.714T.G
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- 2009
34. HLA-DRB1*1501 and Spinal Cord Magnetic Resonance Imaging Lesions in Multiple Sclerosis
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Joep Killestein, Hugo Vrenken, Frederik Barkhof, Antonio Martinez, J. Bart A. Crusius, Madeleine H. Sombekke, Bernard M. J. Uitdehaag, Chris H. Polman, Diego Tejedor, Carsten Lukas, Philip L. De Jager, Dirk L. Knol, A. Salvador Peña, Jeroen J. G. Geurts, David Arteta, Neurology, Epidemiology and Data Science, Pathology, Radiology and nuclear medicine, Physics and medical technology, EMGO - Musculoskeletal health, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases
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Adult ,Male ,Candidate gene ,Pathology ,medicine.medical_specialty ,Multiple Sclerosis ,Central nervous system ,Polymorphism, Single Nucleotide ,Lesion ,Central nervous system disease ,Arts and Humanities (miscellaneous) ,Severity of illness ,medicine ,Humans ,Genetic Association Studies ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Multiple sclerosis ,Brain ,Magnetic resonance imaging ,HLA-DR Antigens ,Middle Aged ,medicine.disease ,Spinal cord ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Spinal Cord ,Female ,Neurology (clinical) ,medicine.symptom ,business ,HLA-DRB1 Chains - Abstract
Multiple sclerosis (MS) is a heterogeneous neurologic disease with extensive variation with respect to the most affected central nervous system region (brain vs spinal cord).To test the hypothesis that this variation in lesion location (brain vs spinal cord) might be (partially) genetically determined.Candidate gene study.Academic research.Patients were selected for the availability of DNA material, clinical variables, and brain and spinal cord magnetic resonance images (evaluating T2-weighted lesion load in the brain and the number of spinal cord lesions).For genotyping, we used a DNA chip containing a set of genes mentioned in previous publications noting their relation to different phenotypes of MS. We assessed the association between brain and spinal cord abnormalities and the genotypes of the patients.One hundred fifty patients were included in the analysis. Five single-nucleotide polymorphisms within the major histocompatibility complex region were associated with the number of focal abnormalities in the spinal cord. The most significant was rs3135388 (surrogate marker for the HLA-DRB1*1501 allele). Carriers of HLA-DRB1*1501 had a median of 4 spinal cord lesions compared with 2 lesions for noncarriers (P.001). No significant association was noted between the single-nucleotide polymorphisms and T2-weighted lesion load in the brain.Carriership of HLA-DRB1*1501 (via rs3135388) was associated with the extent of focal abnormalities in the spinal cord. Spinal cord lesions might be an explanation for increased MS disease severity in patients carrying HLA-DRB1*1501.
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- 2009
35. A Glucocorticoid Receptor Gene Haplotype (TthIII1/ER22/23EK/9 beta) Is Associated with a More Aggressive Disease Course in Multiple Sclerosis
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Lisa M L, van Winsen, Laura, Manenschijn, Elisabeth F C, van Rossum, J Bart A, Crusius, Bart A, Crusius, Jan Willem, Koper, Chris H, Polman, Bernard M J, Uitdehaag, Neurology, Pathology, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, and Internal Medicine
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Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Context (language use) ,Biology ,Biochemistry ,Cohort Studies ,Central nervous system disease ,Receptors, Glucocorticoid ,Immune system ,Glucocorticoid receptor ,Endocrinology ,Polymorphism (computer science) ,Internal medicine ,Perception and Action [DCN 1] ,medicine ,Humans ,Genetic Predisposition to Disease ,Age of Onset ,Polymorphism, Genetic ,Multiple sclerosis ,Biochemistry (medical) ,Haplotype ,Middle Aged ,medicine.disease ,Haplotypes ,Immunology ,Disease Progression ,Female ,Age of onset - Abstract
Context: In patients with multiple sclerosis (MS), glucocorticoids (GCs) might not be sufficiently able to restrain the immune system, possibly due to decreased GC sensitivity. This may be, at least partially, genetically determined. Previously, we reported a more aggressive disease course in patients with the glucocorticoid receptor (GR) gene ER22/23EK polymorphism, which has been shown to decrease GC sensitivity. Objective: In 646 MS patients and 317 healthy controls, we investigated whether haplotypes, including the ER22/23EK polymorphism or the GR 9 beta polymorphism, which is also associated with a relative GC resistance, were associated with a more aggressive disease course. Patients and Methods: Polymorphisms in the GR gene (9 beta, ER22/23EK, TthIIII, BcII, and N363S), which have previously been associated with altered GC sensitivity were determined and haplo-structure was characterized. We evaluated whether the haplotypes were associated with disease susceptibility and several other disease characteristics. The association with disease progression was analyzed using Cox regression with time to Expanded Disability Status Score 6 as outcome. Results: None of the haplotypes was associated with disease susceptibility, age at onset, or onset type. Haplotype 6 (TthIIII, ER2223EK, and 9 beta-G) was associated with a more rapid disease progression (hazard ratio 2.3; 95% confidence interval 1.5-3.7; P < 0.001). This seems to result from the presence of ER22/23EK, and not from the 9 beta and TthIIII polymorphisms. Conclusions: MS patients carrying the haplotype 6 (TthIIII, ER22/23EK, and 9 beta) have a more aggressive disease course. This is probably due to the presence of the polymorphism ER22/23EK, which causes a decreased GC sensitivity. (J Clin Endocrinol Metab 94: 2110-2114, 2009)
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- 2009
36. Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms
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Paul I.W. de Bakker, Alexandra Zhernakova, Willem Verduijn, Jihane Romanos, Alienke J. Monsuur, Renata Auricchio, J. Bart A. Crusius, David A. van Heel, Dalila Pinto, Cisca Wijmenga, Ana Jeremías López, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Pathology, CCA - Oncogenesis, Monsuur, Aj, de Bakker, Pi, Zhernakova, A, Pinto, D, Verduijn, W, Romanos, J, Auricchio, Renata, Lopez, A, van Heel, Da, Crusius, Jb, and Wijmenga, C.
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Linkage disequilibrium ,Public Health and Epidemiology/Screening ,lcsh:Medicine ,Immunology/Autoimmunity ,Single-nucleotide polymorphism ,Genome-wide association study ,Human leukocyte antigen ,Biology ,Genetics and Genomics/Complex Traits ,Polymorphism, Single Nucleotide ,Gastroenterology and Hepatology/Small Intestine ,Cohort Studies ,HLA Antigens ,Risk Factors ,Humans ,Genetic Predisposition to Disease ,lcsh:Science ,Genotyping ,Alleles ,Genetics ,Multidisciplinary ,Haplotype ,lcsh:R ,Case-control study ,nutritional and metabolic diseases ,Tag SNP ,Celiac Disease ,Case-Control Studies ,Immunology ,lcsh:Q ,Research Article - Abstract
Background: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors.Methodology: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations.Conclusion: Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.
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- 2008
37. Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease
- Author
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Jos W. R. Meijer, J. Bart A. Crusius, Muhammed Hadithi, Coen D.A. Stehouwer, Pieter J. Kostense, B. Mary E. von Blomberg, Amado Salvador Peña, Chris J. J. Mulder, Elisabeth Bloemena, Interne Geneeskunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, RS: NUTRIM - R2 - Gut-liver homeostasis, RS: CARIM School for Cardiovascular Diseases, Pathology, Epidemiology and Data Science, and Gastroenterology and hepatology
- Subjects
Test strategy ,Adult ,Male ,medicine.medical_specialty ,Genotype ,Glycoside Hydrolases ,Biopsy ,Enzyme-Linked Immunosorbent Assay ,Disease ,Immunologic Tests ,Gastroenterology ,Gliadin ,Serology ,Internal medicine ,HLA-DQ Antigens ,HLA-DQ ,Intestine, Small ,Internal Medicine ,Medicine ,Humans ,Typing ,Prospective Studies ,Prospective cohort study ,Fluorescent Antibody Technique, Indirect ,Autoantibodies ,Transglutaminases ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,Surgery ,Celiac Disease ,Female ,Gastritis ,medicine.symptom ,business - Abstract
BACKGROUND: Estimates of the diagnostic performance of serologic testing and HLA-DQ typing for detecting celiac disease have mainly come from case-control studies.OBJECTIVE: To define the performance of serologic testing and HLA-DQ typing prospectively.DESIGN: Prospective cohort study.SETTING: University hospital.PATIENTS: Patients referred for small-bowel biopsy for the diagnosis of celiac disease.INTERVENTIONS: Celiac serologic testing (antigliadin antibodies [AGA], antitransglutaminase antibodies [TGA], and antiendomysium antibodies [EMA]) and HLA-DQ typing.MEASUREMENTS: Diagnostic performance of serologic testing and HLA-DQ typing compared with a reference standard of abnormal histologic findings and clinical resolution after a gluten-free diet.RESULTS: Sixteen of 463 participants had celiac disease (prevalence, 3.46% [95% CI, 1.99% to 5.55%]). A positive result on both TGA and EMA testing had a sensitivity of 81% (CI, 54% to 95.9%), specificity of 99.3% (CI, 98.0% to 99.9%), and negative predictive value of 99.3% (CI, 98.0% to 99.9%). Testing positive for either HLA-DQ type maximized sensitivity (100% [CI, 79% to 100%]) and negative predictive value (100% [CI, 98.6% to 100%]), whereas testing negative for both minimized the negative likelihood ratio (0.00 [CI, 0.00 to 0.40]) and posttest probability (0% [CI, 0% to 1.4%]). The addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, did not change test performance compared with either testing strategy alone.LIMITATION: Few cases of celiac disease precluded meaningful comparisons of testing strategies.CONCLUSIONS: In a patient population referred for symptoms and signs of celiac disease with a prevalence of celiac disease of 3.46%, TGA and EMA testing were the most sensitive serum antibody tests and a negative HLA-DQ type excluded the diagnosis. However, the addition of HLA-DQ typing to TGA and EMA testing, and the addition of serologic testing to HLA-DQ typing, provided the same measures of test performance as either testing strategy alone.
- Published
- 2007
38. Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease
- Author
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H. Bas Bueno-de-Mesquita, A. Salvador Peña, J. Bart A. Crusius, Federico Canzian, Petra H.M. Peeters, David G. Cox, and VU University medical center
- Subjects
Adult ,Male ,Adolescent ,Population ,Biology ,digestive system ,Polymorphism, Single Nucleotide ,Inflammatory bowel disease ,Crohn Disease ,Gene Frequency ,medicine ,Humans ,Allele ,education ,Genotyping ,Allele frequency ,Alleles ,Aged ,Netherlands ,education.field_of_study ,Base Sequence ,Haplotype ,Gastroenterology ,Case-control study ,DNA ,General Medicine ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Haplotypes ,Cyclooxygenase 2 ,Case-Control Studies ,Immunology ,Colitis, Ulcerative ,Female ,Brief Reports - Abstract
AIM: Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS: We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5 exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS: Allele 5209G was weakly associated with Crohn's disease (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in patients (3.5%). CONCLUSION: Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.
- Published
- 2005
39. A genomewide screen in a four-generation Dutch family with celiac disease: evidence for linkage to chromosomes 6 and 9
- Author
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Peter L. Pearson, Lodewijk A. Sandkuijl, Martine M. Vrolijk, Roderick H. J. Houwen, J. Bart A. Crusius, Cisca Wijmenga, Jos W. R. Meijer, and Martine J. Van Belzen
- Subjects
Adult ,Male ,Adolescent ,Genetic Linkage ,Disease ,Biology ,Coeliac disease ,Intestinal malabsorption ,Genetic linkage ,medicine ,Humans ,Child ,Aged ,Netherlands ,Genetics ,Linkage (software) ,Aged, 80 and over ,Hepatology ,Genome, Human ,Gastroenterology ,nutritional and metabolic diseases ,Chromosome ,Middle Aged ,medicine.disease ,digestive system diseases ,Pedigree ,Celiac Disease ,Chromosomes, Human, Pair 6 ,Female ,Chromosomes, Human, Pair 9 - Abstract
Celiac disease is caused by the interaction of multiple genes and environmental factors. Inheritance of the disease shows a complex pattern with a 10% sibling recurrence risk. The HLA-region is a major genetic risk locus in celiac disease, but genes outside this region are expected to contribute to the disease risk as well. The aim of this study was to identify the loci causing celiac disease in one large Dutch family with apparent dominant transmission of the disease.The family comprised 17 patients in four generations, with possible transmission of the disease by both grandparents. Microsatellite markers evenly spread over all chromosomes were genotyped and linkage analysis was performed using both dominant and recessive disease models and a model-free analysis.Disease susceptibility in the family was linked to the HLA-region (lod score of 2.33) and all patients were HLA-DQ2. A dominantly inherited non-HLA locus with a maximum lod score of 2.61 was detected at 9p21-13, which was shared by 16 patients. Model-free analysis identified another possible non-HLA locus, at 6q25.3, which was shared by 14 patients (p = 0.01). Neither of these regions was detected in a genomewide screen in Dutch affected sibpairs, but the 9p21 locus has been implicated in Scandinavian families.Two potential non-HLA loci for celiac disease were identified in this large Dutch family. Our results provide replication of the Scandinavian 9p21 locus, and suggest that this locus plays a role in celiac disease patients from different Caucasian populations.
- Published
- 2004
40. The interleukin-1 gene family in multiple sclerosis susceptibility and disease course
- Author
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Bernard M. J. Uitdehaag, Hans M. Schrijver, Frederik Barkhof, Marja L. Laine, J. Bart A. Crusius, Tineke Hooper-van Veen, N. F. Kalkers, Chris H. Polman, Dirk L. Knol, Antoon Zwiers, A. Salvador Peña, and Microbiologie (OUD, ACTA)
- Subjects
Adult ,Male ,Multiple Sclerosis ,Genotype ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Degenerative disease ,Polymorphism (computer science) ,Immunopathology ,medicine ,Humans ,Genetic Predisposition to Disease ,030212 general & internal medicine ,Allele ,Alleles ,Autoimmune disease ,Family Health ,Multiple sclerosis ,Interleukin ,Epistasis, Genetic ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Neurology ,Multigene Family ,Immunology ,Female ,Neurology (clinical) ,030217 neurology & neurosurgery ,Interleukin-1 - Abstract
Multiple sclerosis (MS) is a chronic disease of presumed autoimmune origin with a considerable polygenic influence. We have previously observed that a specific allele combination in genes of the interleukin-1 (IL-1) family influenced the progression rate in MS. We have considerably expanded our patient population (492 MS patients and 228 controls). In the present study, we investigated the role of the IL- 1A - 889, IL-1B - 511, IL-1B+3953 and IL-1RN VNTR gene polymorphisms in MS. In addition, we performed preliminary analyses on longitudinal magnetic resonance imaging (MRI) data. We found no associations between the polymorphisms and susceptibility to MS or clinical features. In addition, we observed no significant effect of the polymorphisms on brain or lesion volumes, Based on our data and those from the literature, one can conclude that there is currently no evidence to support a role for the IL-1 genes in MS.
- Published
- 2003
41. CTLA-4 and CD28 gene polymorphisms in susceptibility, clinical course and progression of multiple sclerosis
- Author
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Tineke van Veen, Bernard M. J. Uitdehaag, J. Bart A. Crusius, Frederik Barkhof, Lisa van Winsen, Bing Xia, Chris H. Polman, A. Salvador Peña, and VU University medical center
- Subjects
Adult ,Genetic Markers ,Male ,Multiple Sclerosis ,Genotype ,Immunology ,chemical and pharmacologic phenomena ,Biology ,Lesion ,Antigen ,CD28 Antigens ,Antigens, CD ,medicine ,Immunology and Allergy ,Humans ,CTLA-4 Antigen ,Genetic Predisposition to Disease ,Longitudinal Studies ,Allele ,Alleles ,Polymorphism, Genetic ,medicine.diagnostic_test ,Multiple sclerosis ,Genetic Carrier Screening ,Brain ,Magnetic resonance imaging ,Epistasis, Genetic ,Middle Aged ,medicine.disease ,Antigens, Differentiation ,Magnetic Resonance Imaging ,Neurology ,Genetic marker ,CTLA-4 ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom - Abstract
The balance between CD28 and CTLA-4 signalling is important for regulation of the immune response. We were interested whether a genetically mediated disturbance of this balance could be related to susceptibility or severity of multiple sclerosis (MS). We examined three polymorphisms in these genes, CTLA-4-318, CTLA-4+49 and CD28-I3+17, in 514 patients with MS and 181 controls. As the loci cannot be assumed independent of each other, we analysed the effects of each of the three polymorphisms corrected for the presence of the other two. We found no association between carriership of any of the alleles either with susceptibility to MS or with clinical features. For a subgroup of patients, longitudinal magnetic resonance imaging (MRI) data were available. We observed no effects of the polymorphisms on brain and lesion volumes. These data suggest that the polymorphisms under investigation do not affect the risk of developing MS and have no influence on the course of disease.
- Published
- 2003
42. Polymorphisms at the TNF locus in Chinese Han population
- Author
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Bing Xia, J. Bart A. Crusius, CS Deng, Bao-Ying Fei, A. Salvador Peña, and You-Qing Zhu
- Subjects
China ,Immunology ,Population ,Locus (genetics) ,Biology ,Gene Frequency ,Ethnicity ,Immunology and Allergy ,Humans ,Allele ,education ,Allele frequency ,Lymphotoxin-alpha ,Alleles ,Genetics ,education.field_of_study ,Polymorphism, Genetic ,Tumor Necrosis Factor-alpha ,Haplotype ,General Medicine ,Haplotypes ,Multigene Family ,Microsatellite ,Gene polymorphism ,Restriction fragment length polymorphism ,Microsatellite Repeats - Abstract
One hundred sixty-four unrelated healthy individuals from Chinese Han population were investigated in order to define the distribution of eight polymorphic loci within the tumor necrosis factor (TNF) gene cluster and determine their relationship between the high polymorphic microsatellite TNFa, b, d, and other elements. The cloning and sequencing for five microsatellites were simultaneously done. In this study, the distribution of TNF alleles apparently vary from other ethnic groups. A new allele was detected and confirmed. It should be emphasized that a very strong association between TNFd8 and TNFe4 is reported and d8e4 haplotype appears to be specific to the population studied. In addition, five extended haplotypes were established in this population: a6b5c1d8e4TNF308-1TNF-betaNco1-1TNFAspH1-2, a2b1c2d5e1TNF308-1TNF-betaNco1-2TNFAspH1-2, a11b4c1d4e3TNF308-1TNF-betaNco1-2TNFAspH1-1, a10b4c1d4e3TNF308-1TNF-betaNco1-2TNFAspH1-1, and a2b3c1d2e3TNF308-2TNFAspH1-2. Data suggest that important ethnic differences may exist and that it is a necessary initiative for further research.
- Published
- 2002
43. Interleukin-12p40 genotype plays a role in the susceptibility to multiple sclerosis
- Author
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Tineke van Veen, Chris H. Polman, G. Bouma, Joep Killestein, Lisa van Winsen, A. Salvador Peña, J. Bart A. Crusius, Hans M. Schrijver, and Bernard M. J. Uitdehaag
- Subjects
Multiple Sclerosis ,Neurology ,Genotype ,Multiple sclerosis ,Immunology ,Interleukin 12p40 ,medicine ,Humans ,Neurology (clinical) ,Biology ,medicine.disease ,Interleukin-12 - Published
- 2001
44. Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome
- Author
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B. Mary E. von Blomberg, Adrie Kromhout, Marije N.L. Wiggers, C.G.D.S. Csizmadia, J. Bart A. Crusius, Anath Oren, A. Salvador Peña, M. Luisa Mearin, and Jan P. Vandenbroucke
- Subjects
Down syndrome ,medicine.medical_specialty ,Glutens ,Cost effectiveness ,Biopsy ,Cost-Benefit Analysis ,Aneuploidy ,Enzyme-Linked Immunosorbent Assay ,Disease ,Gastroenterology ,Coeliac disease ,Serology ,Immunopathology ,Internal medicine ,HLA-DQ Antigens ,Intestine, Small ,medicine ,Humans ,Mass Screening ,Child ,Alleles ,Transglutaminases ,medicine.diagnostic_test ,business.industry ,IgA Deficiency ,medicine.disease ,Immunoglobulin A ,Celiac Disease ,Immunoglobulin G ,Pediatrics, Perinatology and Child Health ,Immunology ,Atrophy ,Down Syndrome ,business ,Follow-Up Studies - Abstract
Objectives: To investigate the best approach to screen for celiac disease (CD) in patients with Down syndrome (DS). Study design: One hundred thirty-seven children with DS were followed up longitudinally. CD screening was offered in 1994, 1996, and 1999 by determination of serum immunoglobulin A–anti-endomysium antibodies (AEA). The HLA-DQA1*0501/DQB1*02 allelic combination known to be strongly positively associated with CD was typed. All IgA-AEA–positive children were given the opportunity to undergo a small bowel biopsy: if villous atrophy was found, the diagnosis of CD was established. Results: CD was diagnosed in 11 (8%) children: 8 in 1994 and 3 in 1996. All of them carried the HLA-DQ alleles associated with CD. The presence of symptoms was not useful in discriminating which children could have CD. Conclusions: Screening once in a lifetime is not enough to detect CD in patients with DS. We propose a new, accurate, and cost-sparing 2-step strategy for screening, based on selection of the individuals with potential CD by HLA-DQ typing and on longitudinal serologic CD screening in this selected group. (J Pediatr 2000;137:756-61)
- Published
- 2000
45. TGFB1 gene polymorphisms and inflammatory bowel disease
- Author
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Gerard Pals, G. Bouma, J. Bart A. Crusius, M. Asunción García-González, Mark H.P. Strunk, Cecilia M. Pérez-Centeno, Stefan G. M. Meuwissen, and A. Salvador Peña
- Subjects
Male ,Polymorphism, Genetic ,Immunology ,Biology ,Bioinformatics ,medicine.disease ,Inflammatory Bowel Diseases ,Inflammatory bowel disease ,Polymerase Chain Reaction ,Human genetics ,Gene Frequency ,Transforming Growth Factor beta ,Genetics ,medicine ,Humans ,Female ,Gene ,Alleles ,Polymorphism, Single-Stranded Conformational - Published
- 2000
46. JAK2 V617F mutation is not involved in thromboembolism in IBD
- Author
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Constantina Coucoutsi, Roel Heijmans, J Bart A Crusius, Ouafae Karimi, Ioannis E. Koutroubakis, A Salvador Peña, Alicia M. Sambuelli, Pathology, and CCA - Immuno-pathogenesis
- Subjects
Adult ,Male ,Adolescent ,Argentina ,Bioinformatics ,Risk Assessment ,Sensitivity and Specificity ,Young Adult ,Crohn Disease ,Thromboembolism ,Humans ,Immunology and Allergy ,Medicine ,Child ,business.industry ,Crohn disease ,Incidence ,Gastroenterology ,Inflammatory Bowel Diseases ,Janus Kinase 2 ,Middle Aged ,Gene Expression Regulation ,Child, Preschool ,Mutation ,Mutation (genetic algorithm) ,Colitis, Ulcerative ,Female ,business ,JAK2 V617F - Published
- 2008
47. Spondyloarthropathy and Idiopathic inflammatory Bowel Diseases
- Author
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S. G. M. Meuwissen, Ben A. C. Dijkmans, Alberta J. Dekker‐Saeys, J. Bart A. Crusius, A. Salvador Peña, and VU University medical center
- Subjects
Ankylosing spondylitis ,HLA-B27 ,Crohn's disease ,medicine.medical_specialty ,Spondyloarthropathy ,business.industry ,Gastroenterology ,Sacroiliitis ,Arthritis ,medicine.disease ,Dermatology ,Psoriatic arthritis ,Immunology ,medicine ,Immunology and Allergy ,Reactive arthritis ,business - Abstract
Spondyloarthropathy (SpA) as observed in patients with idiopathic inflammatory bowel diseases is categorized according to the recently developed criteria of the European Spondylarthropathy Group, and belongs to a large complex of rheumatic disorders, encompassing ankylosing spondylitis, Reiter's disease, psoriatic arthritis, and reactive arthritis. It has been recognized for many years that patients with ulcerative colitis or Crohn's disease frequently have arthritic complications. The gastroenterologist should therefore carefully evaluate any symptom of peripheral or axial arthritis, in an attempt to provide an accurate diagnosis, to define a realistic prognosis, and to establish adequate therapy at an early stage. In this review, clinical and etiopathogenic aspects are analyzed, not only of patients with inflammatory bowel diseases and SpA, but also of patients developing arthritic symptoms after gastrointestinal bacterial infections (reactive arthritis). The significance of ileal mucosal inflammation as observed frequently in patients with SpA is discussed; the contribution of immunogenetic factors in the development of SpA, such as HLA-B27, is briefly reviewed. Finally, analysis is made of the different therapeutic options that are available at present.
- Published
- 1997
48. Sa1252 HLA-Dq9.3 Is a Susceptibility Factor in Celiac Disease Patients With High Titers in a Sensitive Serologic Test in Central China
- Author
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J. Bart A. Crusius, Bing Xia, Guifang Yang, Servaas A. Morré, Hongling Wang, Linjie Luo, Jing Wu, Amado Salvador Peña, Guoying Zhou, and Anlong Yuan
- Subjects
Titer ,Pathology ,medicine.medical_specialty ,Hepatology ,business.industry ,Immunology ,Gastroenterology ,Central china ,Medicine ,Disease ,Human leukocyte antigen ,business ,Serology - Published
- 2013
49. IL-1Bpromoter polymorphism and Epstein-Barr virus in Dutch patients with gastric carcinoma
- Author
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Adriaan J. C. van den Brule, Servaas A. Morré, J. Bart A. Crusius, Behrooz Z. Alizadeh, Laura Murillo, Chris J.L.M. Meijer, Axel zur Hausen, Amado Salvador Peña, and VU University medical center
- Subjects
Herpesvirus 4, Human ,Cancer Research ,Polymorphism, Genetic ,business.industry ,Promoter polymorphism ,Interleukin ,Gastric carcinoma ,medicine.disease_cause ,Epstein–Barr virus ,Virology ,Oncology ,Stomach Neoplasms ,Cancer research ,Humans ,Medicine ,Promoter Regions, Genetic ,business ,Interleukin-1 ,Netherlands - Published
- 2003
50. Sa1331 HLA-DQ Genotype Distribution in Type 1 Diabetes Mellitus Patients With Concomitant Celiac Disease
- Author
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J. Bart A. Crusius, Boudewina M. von Blomberg, Sjoerd F. Bakker, Suat Simsek, Chris J. J. Mulder, and Maarten E. Tushuizen
- Subjects
Type 1 diabetes ,Hepatology ,business.industry ,Concomitant ,Immunology ,HLA-DQ ,Genotype ,Gastroenterology ,Medicine ,Distribution (pharmacology) ,Disease ,business ,medicine.disease - Published
- 2012
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