Aim: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. Methods: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed < 19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. Results: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced significantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15, and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. Conclusion: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.
Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy / A. Latiano, O. Palmieri, M.R. Valvano, R. D'Incà, S. Cucchiara, G. Riegler, A.M. Staiano, S. Ardizzone, S. Accomando, G.L. de Angelis, G. Corritore, F. Bossa, V. Annese. - In: WORLD JOURNAL OF GASTROENTEROLOGY. - ISSN 1007-9327. - 14:29(2008), pp. 4643-4651.
|Titolo:||Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy|
|Parole Chiave:||Autophagy-related 16-like 1; Crohn's disease; Genetic predisposition; Genome-wide association study; Inflammatory bowel disease; Interleukin 23 receptor; Pediatric inflammatory bowel disease; Ulcerative colitis; Gastroenterology|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3748/wjg.14.4643|
|Appare nelle tipologie:||01 - Articolo su periodico|