• Citer

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

par De Jager, P L;Franchimont, Denis ;Waliszewska, A;Bitton, A;Cohen, Aurélie;Langelier, D;Belaiche, Jacques;Vermeire, Séverine;Farwell, L;Goris, An;Libioulle, C;Jani, N;Dassopoulos, T;Bromfield, G P;Dubois, Bertrand ;Cho, Judy H;Brant, S R;Duerr, R H;Yang, Helen;Rotter, J I;Silverberg, M S;Steinhart, A H;Daly, M J;Podolsky, D K;Louis, Edouard;Hafler, D A;Rioux, J D;Quebec IBD Genetics Consortium, ;NIDDK IBD Genetics Consortium,
Référence Genes and immunity, 8, 5, page (387-397)
Publication Publié, 2007-07

Article révisé par les pairs

• Détails
• Contenu

Résumé :

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.