TMEM173、IFNGR1、IFNGR2和IRF8基因单核苷酸多态性与结核病易感性的相关性研究  

Study on the association between single nucleotide polymorphisms in TMEM173,IFNGR1,IFNGR2,and IRF8 genes and susceptibility to tuberculosis

作　　者：黄辉敏 王蕾 程丽平[2] 孙勤[2] 王文娟[1] 杨华[1,2] Huang Huimin;Wang Lei;Cheng Liping;Sun Qin;Wang Wenjuan;Yang Hua(School of Public Health,the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,Guiyang 561113,China;Shanghai Clinical Research Center of Infections Diseases(Tuberculosis),Shanghai Key Laboratory of Tuberculosis,Shanghai Pulmonary Hospital,Tongji University School of Medicine,Shanghai 200433,China)

机构地区：[1]贵州医科大学公共卫生与健康学院,环境污染与疾病监控教育部重点实验室,贵阳561113 [2]同济大学附属上海市肺科医院,上海市结核病(肺)重点实验室,上海市感染性疾病(结核病)临床研究中心,上海200433

出　　处：《中国防痨杂志》2025年第5期629-638,共10页Chinese Journal of Antituberculosis

基　　金：国家重点研发计划(2021YFA1300902);国家自然科学基金(82470001,82270006,82070007);上海市卫生健康委员会青年项目(20204Y0325)。

摘　　要：目的:探讨干扰素基因刺激物(TMEM173)、干扰素γ受体1(IFNGR1)、干扰素γ受体2(IFNGR2)、干扰素调节因子8(IRF8)基因多态性与结核病易感性的相关性。方法:采用病例对照的研究方法,选取2020年1月至2022年12月上海市肺科医院收治的286例肺结核患者(观察组)与同期健康人群484名(对照组)作为研究对象,采集两组人群的外周静脉血进行基因组DNA提取、基因分析和单核苷酸多态性(SNP)筛选,应用SNPscan TM多重SNP分型技术进行基因分型。采用卡方检验比较这些位点的基因型、等位基因和单倍型在观察组和对照组之间的频率分布差异,分析在显性、隐性和超显性遗传模型下各个SNP位点与结核病易感性的关联性。采用多因素logistic回归分析各位点的交互作用与结核病易感性的关联。结果:所有位点等位基因频率分布均符合哈迪-温伯格平衡(Hardy-Weinberg equilibrium,HWE)定律。携带IRF8基因rs8064189位点T等位基因(OR=1.290,95%CI:1.047~1.590,P=0.017)、TT基因型(OR=1.689,95%CI:1.098~2.597,P=0.017)、GT-TT基因型(OR_(显性)=1.231,95%CI:0.999~1.517,P=0.047)和rs8052521位点的CC基因型(OR=1.628,95%CI:1.033~2.565,P=0.035;OR_(隐性)=1.306,95%CI:1.037~1.645,P=0.037),以及该基因CTGAA单倍体型(OR=1.271,95%CI:1.078~1.513,P=0.011)可明显增加结核病的发病风险。携带IFNGR2基因rs9808753位点AG基因型(OR=1.450,95%CI:1.038~2.025,P=0.029)、AA-GG基因型(OR_(超显性)=0.807,95%CI:0.671~0.970,P=0.025)可明显增加结核病发病风险。携带IFNGR1基因TTGG单倍体型(OR=1.160,95%CI:1.014~1.350,P=0.047)可明显增加结核病发病风险。多因素logistic回归分析发现,携带TMEM173基因rs7380824位点CT基因型的个体结核病发病风险提高了1.431倍(OR=1.431,95%CI:1.034~1.979,P=0.031)。未发现其他基因任一位点与结核病易感性的相关性。结论:TMEM173、IFNGR1、IFNGR2、IRF8基因可能为中国人群结核病易感基因。Objective:To investigate the association between genetic polymorphisms in the stimulator of interferon genes(TMEM173),interferon gamma receptor 1(IFNGR1),interferon gamma receptor 2(IFNGR2),and interferon regulatory factor 8(IRF8)and tuberculosis susceptibility.Methods:A case-control study was conducted,including 286 pulmonary tuberculosis cases(Observation group)admitted to Shanghai Pulmonary Hospital from January 2020 to December 2022 and 484 healthy individuals(Control group).Peripheral venous blood was collected from both groups for genomic DNA extraction,genetic analysis and single nucleotide polymorphism(SNP)screening.Genotyping was performed using the SNPscan^(TM)multiplex SNP genotyping assay.Logistic regression and Chi-square tests were used to compare differences in allele,genotype,and haplotype frequencies between the observation and control groups.Associations between SNPs and tuberculosis susceptibility were analyzed under dominant,recessive,and over-dominant genetic models.Multivariate logistic regression was performed to analyze the association between the interaction among SNPs and tuberculosis susceptibility.Results:All SNP allele frequency distributions conformed to Hardy-Weinberg equilibrium.Carriers of the rs8064189 T allele(OR=1.290,95%CI:1.047-1.590,P=0.017),TT genotype(OR=1.689,95%CI:1.098-2.597,P=0.017),GT-TT genotype(OR_(dominant)=1.231,95%CI:0.999-1.517,P=0.047)and rs805252(OR=1.628,95%CI:1.033-2.565,P=0.035;OR_(recessive)=1.306,95%CI:1.037-1.645,P=0.037),as well as the CTGAA haploid type(OR=1.271,95%CI:1.078-1.513,P=0.011)of IRF8 gene significantly increased the tuberculosis risk.Rs9808753 AG genotype(OR=1.450,95%CI:1.038-2.025,P=0.029)and AA-GG genotype(OR_(hyper-dominance)=0.807,95%CI:0.671-0.970,P=0.025)of IFNGR2 gene also significantly increased the risk of tuberculosis.The IFNGR1 TTGG haplotype(OR=1.160,95%CI:1.014-1.350,P=0.047)was linked to increased tuberculosis susceptibility.Multivariate logistic regression revealed that the CT genotype in TMEM173 gene rs7380824 increased the

关 键 词：结核 基因 多态性 单核苷酸 疾病遗传易感性 

分 类 号：R521[医药卫生—内科学]