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

BMC Research Notes

Jyrki J Eloranta³  Gerd A Kullak-Ublick³  Gerhard Rogler⁴  Pawel Gaj¹  Jaroslaw Regula¹  Kaspar Truninger²  Jessica Mwinyi³  Ragam Attinkara³ 

[1] Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education and the Maria Skłodowska Curie Memorial Cancer Center, Institute of Oncology, Warsaw, Poland;Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Switzerland and Division of Gastroenterology, Regional Hospital, Langenthal, Switzerland;Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland;Division of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland

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

Others  :  1165860
DOI  :  10.1186/1756-0500-5-461

 received in 2012-04-26, accepted in 2012-08-01,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Attinkara et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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