Abstract:
BACKGROUND & AIMS:The pregnane X receptor (PXR) regulates an array of genes involved in the response to xenobiotics. Evidence from several studies suggests that xenobiotic metabolism may play a role in inflammatory bowel disease (IBD) and that low levels of PXR may be associated with disease expression. The aim of this study was to investigate the association of functional polymorphisms of the PXR encoding gene (NR1I2) with disease in IBD populations. METHODS:This was a case-control study examining 8 NR1I2 single nucleotide polymorphisms (SNPs) previously associated with altered activity of PXR-regulated genes in an Irish cohort including 422 patients with IBD and 350 ethnically matched controls. RESULTS:We showed significant associations of NR1I2 with IBD, Crohn's disease (CD), and ulcerative colitis (UC) groups compared with a control population for SNPs -23585 (IBD: P = .000008; odds ratio [OR], 1.62; 95% confidence interval [CI], 1.31-2.00) and -24381 (IBD: P = .0002; OR, 1.50; 95% CI, 1.21-1.84). SNPs 7635 (P = .0008) and 8055 (P = .007) were found to be associated with IBD and CD but not UC. Risk of IBD is strongly correlated to genotype at these sites, especially for the -25385CC genotype (P = .00001; OR, 2.92; 95% CI, 1.87-4.66). We also show specific correlations of IBD phenotype with genotypes and haplotypes in the patient group. CONCLUSIONS:These results show that genetic variation in the PXR encoding gene, which has been associated with altered activity of PXR, is strongly associated with susceptibility to IBD, CD, and UC.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Dring MM,Goulding CA,Trimble VI,Keegan D,Ryan AW,Brophy KM,Smyth CM,Keeling PW,O'Donoghue D,O'Sullivan M,O'Morain C,Mahmud N,Wikström AC,Kelleher D,McManus Rdoi
10.1053/j.gastro.2005.12.008keywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
341-8; quiz 592issue
2eissn
0016-5085issn
1528-0012pii
S0016-5085(05)02437-6journal_volume
130pub_type
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