title: Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease.
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, 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.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland.
authors.forename: Ragam
authors.initials: R
authors.lastname: Attinkara
authors.forename: Jessica
authors.initials: J
authors.lastname: Mwinyi
authors.forename: Kaspar
authors.initials: K
authors.lastname: Truninger
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Regula
authors.forename: Pawel
authors.initials: P
authors.lastname: Gaj
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: Jyrki J
authors.initials: JJ
authors.lastname: Eloranta
mesh_terms: D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012307:Risk Factors; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated