Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Dring, M.M. et al.

The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease.

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.[1]

References

The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease. Dring, M.M., Goulding, C.A., Trimble, V.I., Keegan, D., Ryan, A.W., Brophy, K.M., Smyth, C.M., Keeling, P.W., O'Donoghue, D., O'Sullivan, M., O'Morain, C., Mahmud, N., Wikström, A.C., Kelleher, D., McManus, R. Gastroenterology (2006) [Pubmed]

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