The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases
The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases
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DOI：
10.1038/sj.gene.6364398
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发表时间：
2007-07-01
影响因子：
5
通讯作者：
Rioux, J. D.
中科院分区：
文献类型：
--
作者：
De Jager, P. L.;Franchimont, D.;Rioux, J. D.
长期以来，人们一直认为肠道菌群在发起或加剧炎症性肠病（IBD）方面发挥了作用。宿主防御措施，例如Toll样受体（TLR）介导的宿主防御对宿主/病原体的相互作用至关重要，并且与IBD病理生理学有关。为了探索TLR途径中遗传变异与对IBD敏感性的关联，我们对NFKB1和TLR4中假定的IBD风险等位基因进行了复制研究，并进行了分析，我们进行了基于单倍型的IBD屏幕，以与TLR基因的IBD相关性。以及它们的适配器和信号分子的选择。我们对4805例IBD病例的1539例IBD病例的基因分型验证了具有IBD风险的TLR4等位基因的已发表关联（OR）（OR）：1.30，95％置信区间（CI）：1.15-1.48; p = = p = = p = = 0.00017）和克罗恩病（OR：1.33，95％CI：1.16-1.54; p = 0.000035）但不是溃疡性结肠炎。我们还描述了Tirap（OR：1.16，95％CI：1.04-1.30; P = 0.007）的新型暗示证据对IBD风险有适度的影响。因此，我们的分析提供了其他证据，表明TLR4途径 - 在这种情况下，TLR4及其信号分子Tirap-在对IBD的敏感性中起作用。
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.