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.
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.
基金
supported by the"Familien Erichsen Mindefond",the Lundbeck Foundation
the Danish Research Council,the Western Danish Research Forum for Health Science,the County of Viborg,the Danish Colitis-Crohn Association,"John M Klein og hustrus mindelegat"
the A.P. Mφller Foundation for the Advancement of Medical Science
