association of genetic variation in the nr1h4 gene, encoding the nuclear bile acid receptor fxr, with inflammatory bowel disease协会nr1h4遗传变异的基因,编码fxr核胆汁酸受体,与炎症性肠病.pdfVIP

Attinkara et al. BMC Research Notes 2012, 5:461 /1756-0500/5/461 RESEARCH ARTICLE Open Access Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease 1 1 2 3 3 4 Ragam Attinkara , Jessica Mwinyi , Kaspar Truninger , Jaroslaw Regula , Pawel Gaj , Gerhard Rogler , Gerd A Kullak-Ublick1 and Jyrki J Eloranta1* The Swiss IBD Cohort Study Group Abstract Background: 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. Methods: We studied the association of five variants (rs3863377, rs7138843, r rs35724, r of the NR1H4 gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five NR1H4 genetic variants with TaqMan SNP Genotyping Assays. Results: We observed that the NR1H4 SNP rs3863377 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 ris 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). Conclusions: We