| Summary: | <p>Abstract</p> <p>Background</p> <p>Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor, FXR, regulate inflammatory responses and barrier function in the intestinal tract.</p> <p>Methods</p> <p>We studied the association of five variants (<it>rs3863377</it>, <it>rs7138843</it>, <it>rs56163822</it>, <it>rs35724</it>, <it>rs10860603</it>) of the <it>NR1H4</it> gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five <it>NR1H4</it> genetic variants with TaqMan SNP Genotyping Assays.</p> <p>Results</p> <p>We observed that the <it>NR1H4</it> SNP <it>rs3863377</it> is significantly less frequent in IBD cases than in non-IBD controls (allele frequencies: P = 0.004; wild-type vs. SNP carrier genotype frequencies: P = 0.008), whereas the variant <it>rs56163822</it> is less prevalent in non-IBD controls (allele frequencies: P = 0.027; wild-type vs. SNP carrier genotype frequencies: P = 0.035). The global haplotype distribution between IBD and control patients was significantly different (P = 0.003). This also held true for the comparison between non-IBD and UC groups (P = 0.004), but not for the comparison between non-IBD and CD groups (P = 0.079).</p> <p>Conclusions</p> <p>We show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.</p>
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