Journal
INFLAMMATORY BOWEL DISEASES
Volume 11, Issue 4, Pages 331-339Publisher
OXFORD UNIV PRESS INC
DOI: 10.1097/01.MIB.0000158153.71579.b4
Keywords
Crohn's disease; IL1; inflammatory bowel disease; NOD2/CARD15; TNFA
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Background: NOD2/CARD15 was described as the first susceptibility gene to Crohn's disease (CD). Polymorphisms in the TNFA gene and in the IL1 gene cluster, which are associated with an enhanced chronic inflammatory response, may also play a role in the development of CD. The aim of this study was to determine the association of polymorphisms in the CARD15, TNFA, ILIB, and ILIRN genes with risk of development of CD and with the clinicopathological profile of CID patients. Methods: in a case-control study including 235 CD patients and 312 controls (929 controls for TNFA genotyping), the CARD15 (R702W, G908R, and 1007fs), TNFA (-308G/A and -857C/T), ILIB (-51 1C/T), and ILIRIV (intron 2 variable number of tandem repeats) polymorphisms were genotyped. Results: We observed a significant association between CD and the CARD15 polymorphisms, with an odds ratio (OR) of 2.9 [95% confidence interval (Cl), 1.9 to 4.6] for carriers of I variant allele and an OR of 11.8 (95% CI, 3.5 to 40.4) for carriers of 2 variant alleles. Patients with CARD15 polymorphisms had more frequently ileal or ileocolonic disease location, stricturing phenotype, abdominal surgery, and no extraintestinal manifestations. The TNFA-308AIA genotype was associated with susceptibility to CD with an OR of 3.0 (95% CL 1.2 to 7.2). TNFA-308A/A homozygotes showed a higher frequency of erythema nodosum and arthritis, colonic disease location, and absence of abdominal surgery. No associations were found with the TNFA-857, IL1B-511, and the IL1RN VNTR polymorphisms.
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