新疆哈萨克族人群结核病易感基因的病例对照研究

case-control study of gene polymorphisims with susceptibility to tuberculosis in Hazakhs of Xinjiang

目的研究自然抗性相关巨噬细胞蛋白1(NRAMPl)基因3′端非编码区(3′UTR)和维生素D受体(VDR)基因FokI、TaqI位点多态性与新疆哈萨克族人群结核病易感性的关联;分析NRAMPl基因和VDR基因交互作用对新疆哈萨克族人群结核病易感性的影响。方法采用病例对照研究方法,选取新疆哈萨克族活动性肺结核病患者213例,同地区同种族健康者211例。用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)分析方法对NRAMP1基因3′UTR、VDR基因FokI和TaqI多态性位点基因分型,采用2χ检验分析3个位点多态性与新疆哈萨克族结核病易感性的关系,相乘模型分析NRAMPl基因和VDR基因交互作用。结果 1.NRAMPl基因3′UTR位点在病例组和对照组中TGTG/TGTG、TGTG/del和TGT-Gdel/del基因型频率分别为64.8%、29.6%、5.6%和79.1%、19.5%、1.4%。TGTGdel等位基因组间分布差异有统计学意义(χ2=13.737,P<0.01)。2.VDR基因FokI位点在病例组和在对照组中FF、Ff和ff基因型频率分别为33.8%、45.1%、21.1%和47.9%、41.7%、10.4%。f等位基因频率组间分布差异有统计学意义(χ2=13.868,P<0.01);TaqI位点TT、Tt和tt基因型组间分布差异无统计学意义;等位基因T和t组间分布差异无统计学意义(2χ=1.267,P>0.05);D'=0.477,r2=0.01,两位点不存在连锁不平衡。3.NRAMP1基因和VDR基因存在正交互作用,ORint=1.62。结论 1.TGTG/del和TGTGdel/del基因型、TGTG缺失等位基因可能是新疆哈萨克族人群结核病易感基因。2.VDR基因中FokI多态性与新疆哈萨克族结核病易感性有关联,等位基因f可能是新疆哈萨克族结核病易感基因。3.NRAMP1和VDR基因间交互作用可能增加新疆哈萨克族人群结核病的发病风险。

The purpose of this study was to investigate the association between NRAMPl-3′UTR,FokI and TaqI of the VDR gene polymorphisms and susceptibility to tuberculosis of Xinjiang Hazakhs,and analyze the interaction between NRAMP1 gene and VDR gene.Using case-control study,genotyping of the 3′UTR of NRAMP1 gene,FokI and TaqI of VDR gene was done by PCR-RFLP among 213 patients and 211 healthy contacts that had been sensitized to tuberculosis.The association between the three sites and tuberculosis was analyzed using Chi-square test and the interactions between NRAMPl and VDR gene were analyzed by multiple model.Results could be demonstrated as follows： 1.The frequencies of NRAMP-3′UTR TGTG/ TGTG,TGTG/del,and TGTGdel/del genotypes in the case were 64.8%,29.6% and 5.6% respectively,while which were 79.1%,19.5% and 1.4% in the control.The allele frequencies of TGTGdel were statistically significant in tuberculosis group compared with control group（χ2=13.737,P0.01）.2.The frequencies of VDR-FokI FF,Ff and ff genotypes in the case were 47.9%,47.1% and 10.4% respectively,while which were 47.9%,41.7% and 10.4% in the controls.The allele frequencies of f gene were statistically significant in tuberculosis group compared with control group（χ2=13.868,P0.01）.The frequencies of VDR-TaqI tt,Tt and TT genotypes had no statistically significant difference between the case and the control group.The allele frequencies of T and t were not statistically significant in tuberculosis group compared with control group（χ2=1.267,P0.05,D＇=0.477,r2=0.01）.The two polymorphisms of VDR didn＇t show linkage disequilibrium.3.There was positive interaction between VDR-FokI Ff/ff and NRAMPI-3′UTR TGTG/del or TGTGdel/del（ORint=1.62）.It＇s concluded as follows： 1.The Kazakans in Xinjiang carrying TGTG/del or TGTGdel/del genotype are apt to suffertuberculosis;the TGTG del allele might be a risk factor for the tuberculosis of Xinjiang Kazakans.2.The FokI polymorphism of VDR gene might be associated with TB in Hazakhs of Xinjiang;the allele frequencies of gene f might be a risk factor for the tuberculosis of Kazakans in Xinjiang.But no evidences supported that the TaqI polymorphism were associated with TB in Hazakhs of Xinjiang.The two polymorphisms didn＇t show linkage disequilibrium.3.The interaction between NRAMP1 gene and VDR gene might increase tuberculosis incidence of Xinjiang Kazakhs.