학술논문
The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases
Document Type
Academic Journal
Author
De Jager, P L; Franchimont, D; Waliszewska, A; Bitton, A; Cohen, A; Langelier, D; Belaiche, J; Vermeire, S; Farwell, L; Goris, A; Libioulle, C; Jani, N; Dassopoulos, T; Bromfield, G P; Dubois, B; Cho, J H; Brant, S R; Duerr, R H; Yang, H; Rotter, J I; Silverberg, M S; Steinhart, A H; Daly, M J; Podolsky, D K; Louis, E; Hafler, D A; Rioux, J D
Source
Genes and Immunity. Jul 01, 2007 8(5):387-397
Subject
Language
English
ISSN
1466-4879
Abstract
The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15-1.48; P = 0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16-1.54; P = 0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04-1.30; P = 0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD.