TAP1基因多态性与结核病易感关联性的家系病例对照研究  

Association of TAP1 gene polymorphism with susceptibility to tuberculosis:a family case-control study

作　　者：廖寅谦 张开漩 胡宽 骆嘉泽 邹频昂 罗芳 罗丹 汪保国 LIAO Yin-qian;ZHANG Kai-xuan;HU Kuan;LUO Jia-ze;ZOU Pin-ang;LUO Fang;LUO Dan;WANG Bao-guo(Department of Epidemiology,School of Public Health,Guangdong Pharmaceutical University,Guangzhou,Guangdong 510220,China)

机构地区：[1]广东药科大学公共卫生学院流行病学教研室,广东广州510220

出　　处：《现代预防医学》2022年第12期2135-2142,共8页Modern Preventive Medicine

基　　金：广州市科技计划项目(202102080272);广东大学生科技创新培育专项资金项目(pdjha0269)。

摘　　要：目的分析结核病多发家系中TAP1基因rs1135216和rs1057141位点单核苷酸多态性和环境因素与结核病患病的关联,为结核病防治提供理论依据。方法从广东省结核病防治单位纳入结核病多发家庭患者,同病例组有血缘关系的作为家庭密切接触者,另取同期体检的健康人群作为健康对照,共413人纳入本次研究。采用家系病例对照研究方法,通过自行设计的问卷,收集研究对象的一般人口学特征、行为危险因素以及环境因素。采用χ;检验进行单因素分析及Hardy-Weinberg遗传平衡检验,多因素条件logistic回归模型用于分析各因素与结核病患病的关联。应用Haploview软件对两位点进行连锁不平衡分析和单倍型构建。采用GMDR分析基因-基因、基因-环境交互作用对结核病患病的影响。结果共纳入413名研究对象,其中结核病患者(TB)133人,健康对照者(HC)173人,家庭密切接触者(HHC)107人。显性模型分析结果显示,携带CT-CC基因型是结核病患病的危险因素,在HHC组和HC组中,其患病风险分别是携带TT基因型的2.409倍(95%CI:1.377~4.214)和2.014倍(95%CI:1.249~3.247)。单体型分析结果显示,C-T单体型可能是肺结核患病的保护因素。GMDR分析结果显示,基因-基因交互作用在TB组和HC组间的最优模型是rs1135216单因子模型(P<0.05,CVC=10/10,TA=0.579);基因-环境交互作用在TB组和HHC组中,最优模型为rs1135216位点、性别、年龄和文化程度四因子模型(P<0.05,CVC=10/10,TA=0.651);在TB组和HC组中,最优模型为rs1135216位点、文化程度、BMI、居住环境潮湿与否和环境卫生五因子模型(P<0.05,CVC=8/10,TA=0.655)。结论TAP1基因rs1135216位点与结核病患病风险相关,且宿主-环境因素对结核病的发生发展起着重要的作用。Objective To analyze the association between single nucleotide polymorphisms at the rs1135216 and rs1057141loci of the TAP1 gene and environmental factors with tuberculosis(TB)disease prevalence in tuberculosis-prone family lines and to provide a theoretical basis for tuberculosis prevention and treatment.Methods Patients from tuberculosis control institutions in Guangdong Province were included in this study.Those who were related to the case group were selected as close contacts in the family,and healthy people who were examined at the same time were selected as healthy controls.The general demographic characteristics,behavioral risk factors,and environmental factors of the study subjects were collected by a self-designed questionnaire using the family case-control study method.A Chi-square test was used for univariate analysis and Hardy-Weinberg genetic equilibrium test,and a multi-factor conditional logistic regression model was used to analyze the association of each factor with TB disease prevalence.Haploview software was applied to perform linkage disequilibrium analysis and haplotype construction for two loci.GMDR was used to analyze the effects of gene-gene and gene-environment interactions on TB disease prevalence.Results A total of 413 study subjects were included,including 133 tuberculosis patients(TB),173 healthy controls(HC),and 107 close household contacts(HHC).The results of the dominant model analysis showed that carrying the CT-CC genotype was a risk factor for TB disease,and its risk was 2.409(95%CI:1.377-4.214)and 2.014(95%CI:1.249-3.247)times higher than carrying the TT genotype in the HHC and HC groups,respectively.The results of haplotype analysis showed that the C-T haplotype may be a protective factor for TB disease.GMDR analysis showed that the optimal model for gene-gene interaction between TB and HC groups was the rs1135216one-way model(P<0.05,CVC=10/10,TA=0.579).For gene-environment interaction in TB and HHC groups,the optimal model was a four-factor model for rs1135216 locus,sex,age

关 键 词：结核病 抗原处理相关转运蛋白 基因多态性 

分 类 号：R521[医药卫生—内科学]