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The new allele MICA*055 contains eight GCT repeats within the exon 5 MICA-TM microsatellite polymorphism.

Background & Aims Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study. Methodology/Principal Findings Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05–1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06–1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01–1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (p

BACKGROUND: Genome-wide association studies identified PTPN2 (protein tyrosine phosphatase, non-receptor type 2) as susceptibility gene for inflammatory bowel diseases (IBD). However, the exact role of PTPN2 in Crohn's disease (CD) and ulcerative colitis (UC) and its phenotypic effect are unclear. We therefore performed a detailed genotype-phenotype and epistasis analysis of PTPN2 gene variants. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 2131 individuals of Caucasian origin (905 patients with CD, 318 patients with UC, and 908 healthy, unrelated controls) was analyzed for two SNPs in the PTPN2 region (rs2542151, rs7234029) for which associations with IBD were found in previous studies in other cohorts. Our analysis revealed a significant association of PTPN2 SNP rs2542151 with both susceptibility to CD (p = 1.95×10⁻⁵; OR 1.49 [1.34-1.79]) and UC (p = 3.87×10⁻², OR 1.31 [1.02-1.68]). Moreover, PTPN2 SNP rs7234029 demonstrated a significant association with susceptibility to CD (p = 1.30×10⁻³; OR 1.35 [1.13-1.62]) and a trend towards association with UC (p = 7.53×10⁻²; OR 1.26 [0.98-1.62]). Genotype-phenotype analysis revealed an association of PTPN2 SNP rs7234029 with a stricturing disease phenotype (B2) in CD patients (p = 6.62×10⁻³). Epistasis analysis showed weak epistasis between the ATG16L1 SNP rs2241879 and PTPN2 SNP rs2542151 (p = 0.024) in CD and between ATG16L1 SNP rs4663396 and PTPN2 SNP rs7234029 (p = 4.68×10⁻³) in UC. There was no evidence of epistasis between PTPN2 and NOD2 and PTPN2 and IL23R. In silico analysis revealed that the SNP rs7234029 modulates potentially the binding sites of several transcription factors involved in inflammation including GATA-3, NF-κB, C/EBP, and E4BP4. CONCLUSIONS/SIGNIFICANCE: Our data confirm the association of PTPN2 variants with susceptibility to both CD and UC, suggesting a common disease pathomechanism for these diseases. Given recent evidence that PTPN2 regulates autophagosome formation in intestinal epithelial cells, the potential link between PTPN2 and ATG16L1 should be further investigated.

Genome-Wide Association Study for Ulcerative Colitis Demonstrates Novel Associations at Chromosome 22 and 7 Tobias C. Balschun, Andre Franke, Christian Sina, David Ellinghaus, Gabriele Mayr, Mario Albrecht, Michael Wittig, Eva Buchert, Susanna Nikolaus, Christian Gieger, H.Erich Wichmann, Jurgita Sventoraityte, Limas Kupcinskas, Clive Onnie, Maria Gazouli, David P. Strachan, Wendy L. McArdle, Christopher G. Mathew, Paul J. Rutgeerts, Severine Vermeire, Morten H. Vatn, Michael Krawczak, Philip C. Rosenstiel, Tom H. Karlsen, Stefan Schreiber

J. Seiderer1, J. Glas1, J. Diegelmann1, G. Pasciuto1, C. Tillack1, D. Roeske2, S. Pfennig1, M. Jurgens1, A. Konrad1, H. Torok1, T. Griga3, W. Klein4, J.T. Epplen5, U. Schiemann6, T. Mussack7, P. Lohse8, B. Goke1, T. Ochsenkuhn1, M. Folwaczny9, B. Muller-Myhsok10, S. Brand1 *. 1University of Munich Klinikum Groshadern, Munich, Germany, 2Biostatistics, Max-Planck-Institute for Psychiatry, Munich-Schwabing, Munich, Germany, 3Department of Internal Medicine, Knappschaftskrankenhaus Dortmund, Dortmund, Germany, 4Department of Human Genetics, Ruhr-University, Bochum, Germany, 5Department of Human Genetics, University Bochum, Bochum, Germany, 6Department of General Internal Medicine, Inselspital Bern, Bern, Switzerland, 7Department of Surgery, LMU Munich, Munich, Germany, 8Department of Clinical Chemistry, University Hospital Munich-Grosshadern, Munich, Germany, 9Clinic for Preventive Dentistry and Parodontology, LMU Munich, Munich, Germany, 10Max-Planck-Institute for Psychiatry, Munich-Schwabing, Munich, Germany

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S111 colitis (UC) 2 3 cases per 100.000 per year. So far the incidence of pediatric IBD in Hungary is unknown. Methods: The participating institutes are requested to fill out a questionnaire (78 parameters) about every newly diagnosed IBD patients younger than 18 years. The questionnaire is about epidemiological and antropometrical data, main symptoms, diagnostic procedures (endoscopy, CT, MRI), and the detailed results of histological and imaging procedures. Results: Between 01.01.2007 and 30.09.2008 223 newly diagnosed cases of IBD were prospectively identified: 139 cases of CD, 69 cases of UC and 15 cases of indeterminate colitis. As a result the incidence of childhood IBD was 6.13 cases per 100.000, with the incidence of CD being 4.07 cases per 100.000 per year, the incidence of UC 1.67 cases per 100.000 per year and the incidence of indeterminate colitis 0.40 cases per 100.000 per year. The mean age at diagnosis was 13 years (range: 1.5 18 year). There was a male preponderance in CD, in contrast, sex ratio in UC patients were equal. Positive family history of IBD was registered in 7.8% of patients and 9.2% of patients with CD were reported to have a fistula. Ileoscopy rate was only 48% technical problem was the most common reason for the lack of ileal intubation. Oesophagogastro-duodenoscopy was performed in 50% of all cases. In 35% were MRI or CT scan made for the detailed verification of the disease. Conclusions: The incidences reported in the first 21 months of HUPIR are similar to the European and North American data. The dominance of CD proved to be also consistent with other studies. Almost 10% of the patients with CD had fistula. Ileal intubation and oesophago-gastro-duodenoscopy were performed in the half of the cases, and this rate should be improved in the future. P253 The role of pregnane X receptor (PXR/NR1I2) gene variants in inflammatory bowel disease J. Seiderer1 *, J. Glas1, J. Diegelmann1, D. Fischer1, B. Seitz1, S. Pfennig1, T. Griga2, W. Klein3, J.T. Epplen3, U. Schiemann4, T. Mussack5, B. Goke1, T. Ochsenkuhn1, M. Folwaczny6, B. Muller-Myhsok7, S. Brand1. 1University of Munich Klinikum Groshadern, Munich, Germany, 2Department of Internal Medicine, Knappschaftskrankenhaus Dortmund, Dortmund, Germany, 3Department of Human Genetics, Ruhr-University, Bochum, Bochum, Germany, 4Department of General Internal Medicine, Inselspital Bern, Bern, Switzerland, 5University of Munich Department of Surgery, Munich, Germany, 6Clinic for Preventive Dentistry and Parodontology, LMU Munich, Munich, Germany, 7Biostatistics, Max-Planck-Institute for Psychiatry, Munich-Schwabing, Munich, Germany Introduction: The pregnane X receptor (PXR), also known as NR1I2 (nuclear receptor subfamily 1, group I, member 2), is a nuclear receptor encoded by the PXR/NR1I2 gene. The PXR/NR1I2 gene has recently been reported to be associated with susceptibility to inflammatory bowel disease (IBD) (Gastroenterology 2006;130:341 8). However, since a subsequent case-control study failed to replicate this association in an independent population, further replication studies in different ethnic cohorts are required. We therefore investigated this potential association in a large European IBD cohort. Aims and Methods: Genomic DNA from 2823 Caucasian individuals including 859 patients with Crohn’s disease (CD), 464 patients with ulcerative colitis (UC), and 1500 healthy unrelated controls was analyzed for eight single nucleotide polymorphisms (SNPs) in the pregnane X receptor (PXR/NR1I2) gene (rs12721602, rs3814055, rs1523128, rs1523127, rs12721607, rs6785049, rs2276707, rs3814057). Genotyping was performed by PCR and melting curve analysis using a pair of fluorescence resonance energy transfer (FRET) probes in a Light Cycler. Results: With the exception of a weak association of rs2276707 with UC (p = 1.02 x 10 2; OR 1.27 [1.06 1.52]), none of the analyzed variants in the pregnane X receptor (PXR/NR1I2) was associated with susceptibility to CD or to UC in our study population. Conclusion: Our data could not confirm the association of PXR gene variants with CD or UC. Further studies investigating the phenotypic effect and potential epistatic interactions of PXR with other IBD susceptibility genes are required to determine the exact role of PXR in IBD. P254 Incidence of nonspecific ulcerative colitis in Republic of Tatarstan (first Russian inflammatory bowel diseases registry) R.A. Abdulkhakov, S.R. Abdulkhakov*, A.A. Abbakumova. Kazan State Medical University, Kazan, Russian Federation The purpose of the study was to find out the real incidence of nonspecific ulcerative colitis (NUC) in Republic of Tatarstan. Materials and Methods: The registry of NUC patients was made according to case histories and out-patient charts including those who presented with the first onset of the disease as well as those with relapses or stable remission. Results: According to the registry there are 428 NUC patients in Republic of Tatarstan (m-216, 50.47%, f-212, 49.53%, NS). Incidence of NUC is 11.4 per 100000 of population. Acute NUC was revealed in 13 (3%) patients, chronic persistent NUC in 38 (8.9%) patients. Most of the patients (277 pts, 64.7%) had chronic relapsing type of disease which was observed quite often both in males (138 pts) and females (139 pts). In case of 76 patients it was first admission to the hospital due to complaints associated with NUC. In most of patients (150 pts, 35%) distal colitis was observed, in 89 (21%) total colitis, in 32 (7.5%) subtotal, left-sided colitis was found in 125 (29.2%) patients, in case of 32 patients there were no data about the localization of inflammation. According to severity of inflammation distribution of patients was the following: mild inflammation was found in 70 (16.4%) cases, moderate in 237 (55.4%), severe in 61 (14.3%) patient, in case of 60 patient data was lacking. Massive bleeding as a complication of NUC occurred in 10 (2.3%) patients, 4 of them underwent surgery. NUC was the cause of disability in 79 (18.5%) patients. Conclusions: It’s the first registry of NUC patients in Republic of Tatarstan which covered 428 NUC patients and revealed incidence of NUC as 11.4 per 100000 of population. NUC incidence is the same in men and women. Most of patients have distal type of NUC with moderate activity. Frequency of massive bleeding as NUC complication is 2.3%. P255 Anxiety and depression symptoms in Crohn’s disease patients in remission M. Iglesias1, M. Barreiro2 *, A. Figueiras3, M. Vazquez4, L. Nieto1, M. Seoane2, A. Lorenzo2, J.E. Dominguez-Munoz2. 1FIENAD University Hospital, Santiago de Compostela, Spain, 2Gastroenterology University Hospital, Santiago de Compostela, Spain, 3Epidemiology University Hospital, Santiago de Compostela, Spain, 4Clinic Psycology University of Santiago, Santiago de Compostela, Spain Background: Crohn’s disease (CD) is a chronic inflammatory bowel disease with periods of relapse and remission. Role of anxiety and depression in CD patients in remission has been poorly studied. We hypothesized that despite staying in remission, anxiety and depression symptoms have an import role in CD patients. Aim of the study was to evaluate the presence of anxiety and depression symptoms in CD patients in remission and potential by gest on A uust 4, 2016 http://eccoxfordjournals.org/ D ow nladed from