中国异烟肼耐药结核分枝杆菌基因突变特征分析  

Characterisation of isoniazid-resistant Mycobacterium tuberculosis mutations in China

作　　者：徐雁南 方梓昊 赵文丽 郑佳雄 刘苏洋 林健雄 纪丽微 常巧呈 Xu Yannan;Fang Zihao;Zhao Wenli;Zheng Jiaxiong;Liu Suyang;Lin Jianxiong;Ji Liwei;Chang Qiaocheng(School of Public Health,Shantou University,Shantou 515063,China;Shantou Tuberculosis Prevention and Control Institute,Shantou 515041,China)

机构地区：[1]汕头大学公共卫生学院,汕头515063 [2]广东省汕头市结核病防治所,汕头515041

出　　处：《结核与肺部疾病杂志》2025年第1期14-21,共8页Journal of Tuberculosis and Lung Disease

摘　　要：目的:总结异烟肼(INH)耐药结核分枝杆菌菌株耐药基因类型、突变位点、地域差异等方面特征,为结核病的分子生物学诊断、临床用药、耐药基因的新发现等研究提供理论依据。方法:该研究在中国知网、维普、万方数据库中以“异烟肼耐药并且突变并且结核”为检索式检索有关中国结核分枝杆菌耐INH基因突变的研究文献,在PubMed以“Isoniazid OR INH”AND“mutation”AND“Mycobacterium tuberculosis”AND“China”为检索式检索中国相关英文文献,初步检索145篇文献,实际纳入文献22篇,纳入分析菌株12923株,获得INH耐药菌株2824株。以2019年为时间节点,将国内关于INH耐药基因突变信息分为两部分进行研究,对耐药基因类型、突变位点、耐药菌株地域差异等信息进行分析。结果:2019年后,96.18%(2716/2824)检测到INH耐药基因突变,常见突变基因为katG(315位点),占74.49%(1965/2638),以AGC→ACC突变为主,占52.26%(1027/1965);inhA基因-15位点突变最常发生,占13.72%(362/2638),以C→T为主,占89.23%(323/362);1.97%(52/2638)fabG1发生突变。联合突变以katG+inhA突变为主,占2.20%(58/2638)。结论:中国耐INH结核分枝杆菌的耐药基因中,katG、inhA、fabG1基因突变常发,突变位点以katG315、inhA15为主,联合突变以katG+inhA突变为主。Objective:To summarize the mutation characteristics of isoniazid(INH)-resistant strains in terms of drug-resistant gene types,mutation sites and geographical differences,to provide a theoretical basis for the molecular diagnosis of anti-tuberculosis,clinical use of medicines,and the discovery of new drug-resistant genes.Methods:We searched for mutations in INH-resistant genes of Mycobacterium tuberculosis(M.tuberculosis)in China in China Knowledge Network(CNN),Weipu,and Wanfang database with the search terms of“isoniazid resistance”AND“mutation”AND“tuberculosis”,and searched for literature in English with the search terms of“Isoniazid OR INH”AND“mutation”AND“Mycobacterium tuberculosis”AND“China”in PubMed.145 articles were initially identified,22 articles were included,12923 strains were included in the analysis,and 2824 INH-resistant strains were obtained.Taking year 2019 as a time point,the domestic information on INH drug-resistant gene mutations was divided into two parts for studying,then information on drug-resistant gene types,mutation sites,and geographic differences of drug-resistant strains was analyzed in detail.Results:Mutations in INH resistance genes were detected in 96.18%(2716/2824)of strains.The common mutated genes were katG(locus 315),accounting for 74.49%(1965/2638),for which AGC→ACC mutations were predominantly found,accounting for 52.26%(1027/1965).Mutations at locus-15 of the inhA gene were most frequent,accounting for 13.72%(362/2638)with C→T predominating at 89.23%(323/362).fabG1 mutation accounted for 1.97%(52/2638),and the most frequent combined mutation was katG+inhA,accounting for 2.20%(58/2638).Conclusion:Among drug-resistant genes of INH-resistant M.tuberculosis in China,mutations in katG,inhA,and fabG1 gene occured frequently.Mutation loci were dominated by katG315 and inhA15,the most frequent combined mutation was katG+inhA.

关 键 词：分枝杆菌 结核 抗药性 突变 异烟肼 

分 类 号：R183.3[医药卫生—流行病学]