@article{7f2d84b3e586469da10d1ef22fb646e3,
title = "The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases",
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.",
author = "{De Jager}, {P. L.} and D. Franchimont and A. Waliszewska and A. Bitton and A. Cohen and D. Langelier and J. Belaiche and S. Vermeire and L. Farwell and A. Goris and C. Libioulle and N. Jani and T. Dassopoulos and Bromfield, {G. P.} and B. Dubois and Cho, {J. H.} and Brant, {S. R.} and Duerr, {R. H.} and H. Yang and Rotter, {J. I.} and Silverberg, {M. S.} and Steinhart, {A. H.} and Daly, {M. J.} and Podolsky, {D. K.} and E. Louis and Hafler, {D. A.} and Rioux, {J. D.}",
note = "Funding Information: We thank patients with IBD and their families for their collaboration on this project. We also thank Drs Ramnik Xavier and Philippe Goyette for their helpful comments on the manuscript. PLD is the William C Fowler scholar in Multiple Sclerosis and is supported by an NINDS K08 grant as well as the Clinical Investigator Training Program: Harvard-MIT Health Sciences and Technology Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. The authors have no conflicts of interest to report. EL is supported by the FNRS Belgium. AG is a postdoctoral fellow of the Fund for Scientific Research-Flanders and BD is supported by the University Research Council of the University of Leuven, Belgium. JDR is supported by grants from the NIDDK and the CCFA. The authors have no conflict of interest to report.",
year = "2007",
month = jul,
doi = "10.1038/sj.gene.6364398",
language = "English",
volume = "8",
pages = "387--397",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Springer Nature",
number = "5",
}