维生素D受体基因多态性及单倍型与克罗恩病的相关性

摘要

Objective To analyze the association of Crohn's disease(CD)with vitamin D receptor(VDR) gene polymorphisms. Methods After collecting 326 CD patients and 464 healthy controls,the four single nucleotide polymorphisms of VDR (FokI, BsmI, ApaI and TaqI) were examined by a SNaPshot technique. Results Compared with those in controls,the frequencies of mutant allele(A)and genotype(GA+AA)of BsmI were significantly decreased in CD patients(both P=0.001). The similar conclusions were also drawn for the mutant allele(C)and genotype(TC+CC)of TaqI(both P<0.05). In further stratified analysis,compared with those in controls,the mutant alleles and genotypes of BsmI and TaqI were significantly reduced in stenotic type CD patients (all P<0.0083). The analyses of linkage disequilibrium(LD)and haplotype showed that BsmI,ApaI and TaqI were in a strong LD,and the formed haplotype AAC was significantly lower in CD patients than that in controls (P <0.05). Conclusions VDR(BsmI and TaqI)polymorphisms are significantly related with the reduced susceptibility to CD,especially for patients with stenotic CD. Moreover,the haplotype AAC might engender a reduced risk of CD.%目的:探讨维生素D受体(VDR)基因多态性与克罗恩病(CD)的关系.方法:在326例CD患者和464名对照者中,采用SNaPshot技术检测VDR(FokI,BsmI,ApaI、TaqI)4种单核苷酸多态性.结果:与对照组相比,CD组中BsmI的突变等位基因(A)和基因型(GA+AA)频率显著降低(均P=0.001);TaqI的突变等位基因(C)和基因型(TC+CC)频率亦显著降低(均P<0.05).分层分析显示与对照组相比,狭窄型CD患者中BsmI和TaqI的突变等位基因和基因型频率亦显著降低(均P<0.0083).随后的单倍型分析显示BsmI、ApaI和TaqI彼此紧密连锁,CD组中AAC单倍型频率显著低于对照组(P<0.05).结论:VDR(BsmI、TaqI)基因突变可能降低CD,尤其是狭窄型CD的发病风险.AAC单倍型携带者罹患CD的风险性可能降低.