Polymorphisms in NF-κB,PXR,LXR,PPARγ and risk of inflammatory bowel disease

摘要

AIM:To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease(IBD) . METHODS:Genotypes of nuclear factor(NF) -κB(NFKB1) NFκB-94ins/del(rs28362491) ;peroxisome proliferatoractivated receptor(PPAR) -γ(PPARγ) PPARγPro12Ala(rs1801282) and C1431T(rs 3856806) ;pregnane X receptor(PXR) (NR1I2) PXR A-24381C(rs1523127) ,C8055T(2276707) ,and A7635G(rs 6785049) ;and liver X receptor(LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients,495 ulcerative colitis(UC) patients,and 779 healthy controls.Odds ratio(OR) and 95%CI were estimated by logistic regression models. RESULTS:The PXR A7635G variant,the PPARγPro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC(OR:1.31,95% CI:1.03-1.66,P=0.03,OR:2.30,95%CI:1.04-5.08,P=0.04,and OR:1.41,95%CI:1.00-1.98,P=0.05,respectively) compared to the corresponding homozygous wild-type genotypes.Among never smokers,PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD(OR:1.41,95%CI:1.05-1.91,P=0.02,OR:1.63,95%CI:1.21-2.20,P=0.001,and OR:2.02,95%CI:1.36-2.99,P=0.0005,respectively) compared to the respective homozygous variant genotypes.PXR A7635G(rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease(OR:1.34,95%CI:1.03-1.75 and OR:2.49,95%CI:1.24-5.03,respectively) . CONCLUSION:Common PXR and LXR polymorphisms may contribute to risk of IBD,especially among never smokers.