BACKGROUND: The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case-control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population. METHODS: Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at -25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CD patients and compared with 550 ethnically matched controls. RESULTS: The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; chi(2) = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; chi(2) = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20-2.30). Patients with extensive UC carrying the -25385T allele showed increased susceptibility compared with left-sided colitis patients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the -25385T risk allele (P = 0.005). CONCLUSIONS: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.
BACKGROUND: The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case-control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population. METHODS: Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at -25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CDpatients and compared with 550 ethnically matched controls. RESULTS: The overall haplotypic distribution showed a significant difference between UC and CDpatients (P = 0.05; chi(2) = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; chi(2) = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20-2.30). Patients with extensive UC carrying the -25385T allele showed increased susceptibility compared with left-sided colitispatients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the -25385T risk allele (P = 0.005). CONCLUSIONS: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.
Authors: Tristan M Sissung; Sarah M Troutman; Tessa J Campbell; Heather M Pressler; Hyeyoung Sung; Susan E Bates; William D Figg Journal: Discov Med Date: 2012-01 Impact factor: 2.970
Authors: Rita Piedade; Elke Schaeffeler; Stefan Winter; Sara Asimus; Matthias Schwab; Michael Ashton; Oliver Burk; José P Gil Journal: Antimicrob Agents Chemother Date: 2012-01-17 Impact factor: 5.191
Authors: Jason Moore; Amy Jayne McKnight; Bernd Döhler; Matthew J Simmonds; Aisling E Courtney; Oliver J Brand; David Briggs; Simon Ball; Paul Cockwell; Christopher C Patterson; Alexander P Maxwell; Stephen C L Gough; Gerhard Opelz; Richard Borrows Journal: J Am Soc Nephrol Date: 2012-10-11 Impact factor: 10.121
Authors: Aditya Garg; Angela Zhao; Sarah L Erickson; Subhajit Mukherjee; Aik Jiang Lau; Laurie Alston; Thomas K H Chang; Sridhar Mani; Simon A Hirota Journal: J Pharmacol Exp Ther Date: 2016-07-20 Impact factor: 4.030