河南省维生素D受体基因rs2222570和rs731236位点多态性与结核病的易感性

Association of polymorphisms of rs2222570 and rs731236 in vitamin D receptor gene with tuberculosis susceptibility in Henan Province

目的:探讨河南省人群维生素D受体(VDR)基因多态性和结核病易感性之间关系。方法:采用病例对照研究方法,病例组纳入260个结核病患者,并以年龄和性别相匹配纳入260名健康人作为对照组。采用PCR-SSCP法对VDR基因位点多态性进行分析。应用SPSS 19.0对数据进行统计分析,SHEsis在线分析2个位点单倍体型和结核病发病的关联,MDR软件3.0.2分析基因和环境交互作用对结核病发病的影响。结果:VDR基因rs2222570位点多态性与结核病发病风险相关,野生型C/C降低了结核病发病50%的风险(校正OR=0.501,95%CI:0.343~0.709),并且该位点等位基因C在对照组中高于病例组(校正OR=0.632,95%CI:0.493~0.868);而VDR基因的rs731236位点突变基因型C/C增加结核病发病风险(校正OR=2.001,95%CI:1.838~2.191)。VDR基因单倍体型CT、TT和TC与结核病发病相关[CT:OR(95%CI)=0.673(0.521~0.847),P<0.001;TT:OR(95%CI)=1.332(1.043~1.711),P=0.032;TC:OR(95%CI)=6.561(2.366~18.143),P<0.001]。MDR结果表明VDR基因rs2222570和rs731236位点多态性、吸烟、结核病患者密切接触史4个因素交互作用增加了结核病发病风险[OR(95%CI)=7.619(2.201~26.354),P<0.001]。结论:VDR基因多态性与结核病发病风险相关,且VDR基因rs2222570和rs731236位点多态性、吸烟、结核病患者密切接触史存在交互作用。

Aim： To evaluate whether the vitamin D receptor（ VDR） gene polymorphism or its haplotypes might be associated with tuberculosis susceptibility in Henan Han population. Methods： A total of 260 patients with tuberculosis were recruited,and 260 healthy control matched by sex and age were chosen. Genetic polymorphisms of rs2222570 and rs731236 in VDR gene were analyzed using PCR-SSCP. The data were analyzed by SPSS 19. 0. The comparison of haplotypes were carried out by SHEsis online. The MDR 3. 0. 2 software was applied to analyze gene-environment interaction on the risk of tuberculosis susceptibility. Results： The variant genotypes of rs2222570 in VDR gene were significantly associ-ated with the risk of tuberculosis,and the risk of individuals carrying wildtype genotype C/C decreased by 50%（ adjusted OR = 0. 501,95% CI： 0. 343-0. 709）. The frequency of allele C in rs2222570 locus was significantly higher in control group compared with the tuberculosis group（ adjusted OR = 0. 632,95% CI： 0. 493-0. 868）. Whereas the mutant genotype C/C of VDR gene rs731236 polymorphism increased the risk of tuberculosis（ adjusted OR = 2. 001,95% CI： 1. 838-2. 191）. Haplotype analysis showed significant differences in the frequency of haplotype CT,TT,and TC between the two groups[CT： OR（ 95% CI） = 0. 673（ 0. 521-0. 847）,P〈0. 001; TT： OR（ 95% CI） = 1. 332（ 1. 043-1. 711）,P =0. 032; TC： OR（ 95% CI） = 6. 561（ 2. 366-18. 143）,P〈0. 001]. The interaction of the four factor model,rs2222570,rs731236 of VDR genotypes polymorphisms,smoking and the history of exposure to tuberculosis,might increase the risk of tuberculosis [OR（ 95% CI） = 7. 619（ 2. 201-26. 354）,P〈0. 001]. Conclusion： The polymorphism of rs2222570 and rs731236 in VDR gene are associated with the risk of tuberculosis,and there may be significant interaction between the rs2222570,rs731236 of VDR genotypes polymorphisms,smoking and history of exposure to tuberculosis.