Journal Article

Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease

Regula, Jaroslaw, Mwinyi, Jessica, Gaj, Pawel, Rogler, Gerhard, Eloranta, Jyrki J, Truninger, Kaspar, Attinkara, Ragam, Kullak-Ublick, Gerd A

2012

Overview

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 , rs56163822 , rs35724 , rs10860603 ) 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 rs56163822 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). Conclusions We show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acids / Adult / Aged / Analysis / Bile / Bile acid homeostasis / Biomedical and Life Sciences / Biomedical research / Biomedicine / Colitis, Ulcerative - genetics / Colleges & universities / Confidence intervals / Crohn Disease - genetics / Crohn’s disease / Deoxycholic acid / Farnesoid X receptor / Female / Gallbladder diseases / Gene expression / Gene Frequency / Genes / Genetic aspects / Genetic Predisposition to Disease - genetics / Genetics / Genotype / Haplotypes / Hepatology / Hospitals / Humans / Immune response / Inflammation / Inflammatory bowel disease / Inflammatory Bowel Diseases - genetics / Life Sciences / Linkage Disequilibrium / Male / Medicine/Public Health / Middle Aged / Nitric oxide / Pathogenesis / Polymorphism, Single Nucleotide / Proteins / Receptors, Cytoplasmic and Nuclear - genetics / Research Article / Risk Factors / Rodents / Single nucleotide polymorphisms / Sterols / Ulcerative colitis