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

P. L. De Jager, 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. RotterM. S. Silverberg, A. H. Steinhart, M. J. Daly, D. K. Podolsky, E. Louis, D. A. Hafler, J. D. Rioux

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114 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)387-397
Number of pages11
JournalGenes and Immunity
Volume8
Issue number5
DOIs
StatePublished - Jul 1 2007

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ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

Cite this

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., ... Rioux, J. D. (2007). The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes and Immunity, 8(5), 387-397. https://doi.org/10.1038/sj.gene.6364398