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1. Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease.

Author

Latiano A, Palmieri O, Corritore G, Valvano MR, Bossa F, Cucchiara S, Castro M, Riegler G, De Venuto D, D'Incà R, Andriulli A, and Annese V

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Autophagy-Related Proteins, Carrier Proteins genetics, Child, Child, Preschool, Colitis, Ulcerative pathology, Crohn Disease pathology, Female, GTP-Binding Proteins genetics, Genetic Association Studies, Genotype, Haplotypes genetics, Humans, Infant, Male, Middle Aged, Nod2 Signaling Adaptor Protein genetics, Phenotype, Receptors, Interleukin genetics, Young Adult, Chromosomes, Human, Pair 3 genetics, Colitis, Ulcerative genetics, Crohn Disease genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics
Abstract

Background: To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation., Methods: In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis <19 years of age, and 651 controls were analyzed for SNPs rs9858542 and rs3197999., Results: BSN and MST1 were significantly associated with either CD (P(rs9858542) 2.5 x 10(-7); P(rs3197999) 3.9 x 10(-7)), and UC (P(rs9858542) = 3.1 x 10(-4); P(rs3197999) = 8 x 10(-4)). Prevalence of these variants was significantly increased in both adult and early-onset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (P(rs9858542) = 0.013, odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.16-3.59; P(rs3197999) = 0.018, OR 1.9, 95% CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95% CI 0.4-0.9)., Conclusions: We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.

Published
2010
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2. Polymorphisms of tumor necrosis factor-alpha but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease

Author

Cucchiara, Salvatore, Latiano, A, Palmieri, O, Canani, Rb, D'Inca, R, Guariso, G, Vieni, G, DE VENUTO, D, Riegler, G, De'Angelis, Gl, Guagnozzi, D, Bascietto, C, Miele, E, Valvano, Mr, Bossa, F, Annese, V, and ITALIAN SOCIETY OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION

Subjects
Adult, Male, medicine.medical_specialty, Necrosis, Adolescent, Nod2 Signaling Adaptor Protein, Azathioprine, Inflammatory bowel disease, Gastroenterology, chemistry.chemical_compound, Mesalazine, Crohn Disease, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, ATP Binding Cassette Transporter, Subfamily B, Member 1, Glucocorticoids, Polymorphism, Genetic, business.industry, Tumor Necrosis Factor-alpha, medicine.disease, Inflammatory Bowel Diseases, Mercaptopurine, Ulcerative colitis, digestive system diseases, Infliximab, chemistry, Pediatrics, Perinatology and Child Health, Immunology, Tumor necrosis factor alpha, Colitis, Ulcerative, Female, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract

We investigated the contribution of variants of tumour necrosis factor (TNF)-alpha and MDR1 genes in the predisposition and response to medical therapy in a large pediatric cohort of patients with Crohn disease (CD) and ulcerative colitis (UC).In this study, 200 patients with CD, 186 patients with UC, 434 parents (217 trios), and 347 healthy unrelated controls were investigated. Single-nucleotide polymorphisms -G308A and -C857T of the TNF-alpha gene and C3435T of the MDR1 gene were investigated and correlated with clinical subphenotypes and efficacy of medical therapy.The frequency of the -308A allele of the TNF-alpha gene was significantly increased in both patients with CD (15%; odds ratio [OR] = 2.79; P0.01) and patients with UC (11%; OR = 1.96; P0.003) compared with controls (6%). Carriers of this allele were 27% in CD (OR = 2.94; P0.01) and 19% in UC (OR = 1.86; P = 0.015) compared with 11% in healthy controls. No significant difference was found for both the -C857T and C3435T single-nucleotide polymorphisms. With the genotype/phenotype analysis, no correlation in patients with UC with the MDR1 gene was found. CD carriers of the -308A allele had a higher frequency of surgical resection (35% vs 20%; OR = 2.1; P = 0.035) and more frequent resistance to steroids (22% vs 8%; OR = 0.29; P = 0.032) compared with noncarriers. These findings were confirmed by stepwise logistic regression.In our pediatric cohort, the promoter -308A polymorphism of TNF-alpha but not the MDR1 gene is significantly involved in the predisposition to both CD and UC. This polymorphism carries a significant reduction in response to steroid therapy, probably leading to a more frequent need for surgical resection.

Published
2007

3. Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease

Author

Renata D'Incà, Angelo Andriulli, Anna Latiano, Salvatore Cucchiara, Domenica De Venuto, Maria Rosa Valvano, Vito Annese, Massimo Castro, Giuseppe Corritore, Gabriele Riegler, Fabrizio Bossa, Orazio Palmieri, Latiano, A, Palmieri, O, Corritore, G, Valvano, Mr, Bossa, F, Cucchiara, S, Castro, M, Riegler, Gabriele, DE VENUTO, D, D'Inca', R, Andriulli, A, and Annese, V.

Subjects
Adult, Male, Adolescent, Genotype, crohn's disease, Nod2 Signaling Adaptor Protein, Autophagy-Related Proteins, Single-nucleotide polymorphism, Inflammatory bowel disease, Polymorphism, Single Nucleotide, BSN, MST1, ulcerative colitis, Crohn’s disease, Young Adult, Gene interaction, Crohn Disease, GTP-Binding Proteins, NOD2, medicine, Immunology and Allergy, Humans, Genetic Predisposition to Disease, Child, genotype/phenotype, Genetic Association Studies, ulcerative colitis, Aged, Aged, 80 and over, Crohn's disease, business.industry, Gastroenterology, Infant, mst1, Odds ratio, Receptors, Interleukin, Middle Aged, medicine.disease, Ulcerative colitis, digestive system diseases, bsn, Phenotype, Haplotypes, Child, Preschool, Cohort, Immunology, Colitis, Ulcerative, Female, Chromosomes, Human, Pair 3, business, Carrier Proteins
Abstract

Background: To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene–gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype–phenotype correlation. Methods: In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis

Published
2009

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