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

被引：45
作者：
Ragam Attinkara
Jessica Mwinyi
Kaspar Truninger
Jaroslaw Regula
Pawel Gaj
Gerhard Rogler
Gerd A Kullak-Ublick
Jyrki J Eloranta
机构：
[1] Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich
[2] Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel
[3] Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Institute of Oncology, Warsaw
[4] Division of Gastroenterology and Hepatology, University Hospital, Zurich
[5] Division of Gastroenterology, Regional Hospital, Langenthal
来源：
BMC Research Notes | / 5卷 / 1期
关键词：
Bile acid homeostasis; Crohns disease; Farnesoid X receptor; Inflammatory bowel disease; Single nucleotide polymorphisms; Ulcerative colitis;
D O I：
10.1186/1756-0500-5-461
中图分类号：
学科分类号：
摘要：
Background: Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohns 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. © 2012 Attinkara et al.; licensee BioMed Central Ltd.
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