Open Access Research article

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

Ragam Attinkara1, Jessica Mwinyi1, Kaspar Truninger2, Jaroslaw Regula3, Pawel Gaj3, Gerhard Rogler4, Gerd A Kullak-Ublick1, Jyrki J Eloranta1* and The Swiss IBD Cohort Study Group

Author Affiliations

1 Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland

2 Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Switzerland and Division of Gastroenterology, Regional Hospital, Langenthal, Switzerland

3 Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education and the Maria Skłodowska Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland

4 Division of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland

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BMC Research Notes 2012, 5:461  doi:10.1186/1756-0500-5-461

Published: 28 August 2012



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.


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.


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).


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

Bile acid homeostasis; Crohn’s disease; Farnesoid X receptor; Inflammatory bowel disease; Single nucleotide polymorphisms; Ulcerative colitis