The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases - PubMed (original) (raw)

doi: 10.1038/sj.gene.6364398. Epub 2007 May 31.

D Franchimont, A Waliszewska, A Bitton, A Cohen, D Langelier, J Belaiche, S Vermeire, L Farwell, A Goris, C Libioulle, N Jani, T Dassopoulos, G P Bromfield, B Dubois, J H Cho, S R Brant, R H Duerr, H Yang, J I Rotter, M S Silverberg, A H Steinhart, M J Daly, D K Podolsky, E Louis, D A Hafler, J D Rioux; Quebec IBD Genetics Consortium; NIDDK IBD Genetics Consortium

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The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases

P L De Jager et al. Genes Immun. 2007 Jul.

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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.

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