VDR基因多态性与耐多药肺结核的关联  

Association between VDR Gene Polymorphism and Multidrug-resistant Tuberculosis

作　　者：刘幸 孙辉 杜映荣 陈洁 欧阳兵 张乐 LIU Xing;SUN Hui;DU Ying-rong;CHEN Jie;OUYANG Bing;ZHANG Le(Dept.of Pharmacy,The 3rd People's Hospital of Kunming,Kunming Yunnan 650041,China;Dept.of Critical Care Medicine,The 3rd People's Hospital of Kunming,Kunming Yunnan 650041,China;Dept.of Tuberculosis,The 3rd People's Hospital of Kunming,Kunming Yunnan 650041,China)

机构地区：[1]昆明市第三人民医院药剂科,云南昆明650041 [2]昆明市第三人民医院重症医学科,云南昆明650041 [3]昆明市第三人民医院结核科,云南昆明650041

出　　处：《昆明医科大学学报》2020年第3期22-29,共8页Journal of Kunming Medical University

基　　金：昆明市科技局科技计划重点项目(2017-1-S-14333)。

摘　　要：目的探讨云南地区汉族人群VDR基因FokI、TaqI位点单核苷酸多态性与耐多药肺结核发生的关系,并寻找基因型的影响因素。方法应用聚合酶链式反应检测VDR基因FokI、TaqI位点的多态性,比较感染组(耐多药肺结核患者)与对照组(健康体检人群)基因型的分布频率和等位基因的频率差异,并对感染组基因型的影响因素进行二分类Logistic回归分析。结果300例感染组与300例对照组VDR基因FokI位点的基因型FF分布频率为29.8%/33.0%,基因型Ff分布频率为45.5%/53.3%,基因型ff分布频率24.7%/13.7%,两组比较χ^2=11.783,P=0.003。等位基因F分布频率52.5%/59.7%,等位基因f分布频率47.5%/40.3%,两组比较χ^2=6.256,P=0.012。VDR基因TaqI位点的基因型TT分布频率为55.8%/61.7%,基因型Tt分布频率为36.4%/32.7%,基因型tt分布频率7.8%/5.6%,两组比较χ^2=2.700,P=0.259。等位基因T分布频率73.8%/78.0%,等位基因t分布频率26.2%/22.0%,两组比较χ^2=2.849,P=0.091。VDR基因FokI位点的基因型ff增加了耐多药肺结核的易感性(OR:2.008,95%CI:1.246,3.235),等位基因f亦增加了其的易感性(OR:1.388,95%CI:1.065,1.682)。但VDR基因TaqI位点多态性与耐多药肺结核易感性无关。在影响因素分析中,患者的依从性(OR=2.583,95%Cl=1.342~4.287)、药物的不良反应(OR=0.162,95%Cl=0.094~0.432)、合并结核性胸膜炎(OR=0.249,95%Cl=0.026~0.278)是VDR基因FokI位点基因突变的影响因素。结论云南汉族人群耐多药肺结核的发生与VDR基因FokI位点的多态性有关,与TaqI位点多态性无关,而患者的依从性、药物不良反应、合并结核性胸膜炎可能与FokI位点突变有关。Objective To explore the relationship between VDR gene FokI,TaqI single nucleotide polymorphism and MDR-resistant tuberculosis in Yunnan Han population and to find out the influencing factors of VDR genotype.Methods Polymorphism of VDR gene at FokI,TaqI was detected by PCR.The differences of distribution and allele frequency of VDR gene at FokI,TaqI genotypes were compared between the tuberculosis group(n=300)and the control group(n=300).Two-class logistic regression analysis of genotypes was conducted in tuberculosis group.Results In FokI locus of VDR gene,the distribution frequency of genotype FF,genotype Ff and genotype ff were 29.8%/33.0%,45.5%/53.3%and 24.7%/13.7%respectively and there was significant difference between the two groups(χ^2=11.783,P=0.003).The distribution frequency of allele F and allele f were 52.5%/59.7%and 47.5%/40.3%respectively and there was significant difference between the two groups(χ^2=6.256,P=0.012).In TaqI locus of VDR gene,the distribution frequency of genotype TT,genotype Ttandgenotype tt were 55.8%/61.7%,36.4%/32.7%and 7.8%/5.6%respectively and there was no significant difference between the two groups(χ^2=2.700,P=0.259).The distribution frequency of allele T and allele t were 73.8%/78.0%and 26.2%/22.0%respectively and there was no significant difference between the two groups(χ^2=2.849,P=0.091).The genotype ff of FokI in VDR gene increased the susceptibility of MDR-TB(OR:2.008,95%CI:1.246,3.235),and the allele f also increased the susceptibility(OR:1.388,95%CI:1.065,1.682).But the TaqI polymorphism of VDR gene was not related to the susceptibility of MDR-TB.Logistic regression analysis showed that compliance(OR=2.583,95%Cl=1.342-4.287),adverse drug reactions(OR=0.162,95%Cl=0.094-0.432)and tuberculous pleurisy(OR=0.249,95%Cl=0.026-0.278)were three factors influencing the FokI gene mutation of VDR gene.Conclusions The occurrence of MDR-TB in Yunnan Han population is related to the polymorphism of FokI locus of VDR gene,but not to the polymorphism of TaqI locus.The patient’

关 键 词：维生素D 基因多态性 结核病 多因素分析 

分 类 号：R521[医药卫生—内科学]