广西地区结核分枝杆菌异烟肼耐药基因突变特征分析
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1.广西中医药大学公共卫生与管理学院, 广西 南宁 530200;2.广西江滨医院检验科, 广西 南宁 530021;3.广西壮族自治区疾病预防控制中心结核病防制所, 广西 南宁 530021

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罗丹  E-mail: Luodan.2005@163.com

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基金项目:

广西自然科学基金面上项目(2017GXNSFAA198330);广西中医药大学博士科研启动项目(2017BS004);广西中医药大学研究生创新项目(YCSW2021226);广西医疗卫生适宜技术开发与推广应用项目(S2017066)


Mutation characterization of isoniazid resistance genes of Mycobacterium tuberculosis in Guangxi region
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1.Academy of Public Health and Management, Guangxi University of Chinese Medicine, Nanning 530200, China;2.Department of Clinical Laboratory, Guangxi Jiangbin Hospital, Nanning 530021, China;3.Institute for Tuberculosis Control, Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning 530021, China

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    摘要:

    目的 分析广西地区结核分枝杆菌异烟肼(INH)耐药基因的突变特征,为耐药结核病的分子诊断提供依据。 方法 选取2018年广西30个结核病耐药监测点收集的结核分枝杆菌菌株库中122株耐INH菌株和530株全敏感菌株进行全基因组测序。 结果 652株结核分枝杆菌复合群菌株中,127株(19.48%)发生INH耐药基因突变,分别为katG(15.64%,102株)、fabG1(1.69%,11株)、ahpC(1.07%,7株)、kasA(0.61%,4株)和inhA(0.46%,3株)基因突变。INH耐药表型与基因突变的符合率为90.03%,比例法药敏检测INH耐药与基因测序检测基因突变结果吻合度不高(Kappa=0.677)。突变类型共有19种,单位点突变占96.85%,联合位点突变占3.15%。突变比率最高的位点为katG315(71.65%),碱基变化以AGC-ACC形式占比最高(12.13%)。katG、ahpC和kasA基因突变比例在INH耐药株中高于敏感株(均P < 0.05),INH耐药株和敏感株inhA、fabG1基因突变比例比较,差异均无统计学意义(均P>0.05)。北京株、非北京株中katG315突变率最高,分别为18.75%(81/432)、4.55%(10/220),两种基因型菌株katG基因突变位点分布比较,差异有统计学意义(χ2=16.253,P=0.039)。 结论 广西地区INH耐药基因突变以katG315位点突变为主,INH耐药表型与基因突变吻合度不高。katG、ahpC与kasA基因突变与INH表型耐药有相关性。北京基因型与katG基因的突变有相关性。

    Abstract:

    Objective To analyze the mutation characteristics of isoniazid (INH) resistance gene of Mycobacterium tuberculosis (MTB)in Guangxi region, and provide basis for molecular diagnosis of drug-resistant tuberculosis. Methods 122 INH-resistant strains and 530 susceptible strains were obtained from the MTB strain library collected from 30 tuberculosis drug resistance monitoring points in Guangxi region, and underwent whole genome sequencing. Results Among 652 strains of MTB complex group, 127 (19.48%) had INH resistance gene mutations, including katG (15.64%, n=102), fabG1 (1.69%, n=11), ahpC (1.07%, n=7), kasA (0.61%, n=4) and inhA (0.46%, n=3) gene mutations. The coincidence rate of INH resistance phenotype and gene mutation was 90.03%, and the coincidence rate of INH resistance detected by proportional method and gene mutation detected by gene sequencing was not high (Kappa=0.677). There are 19 types of mutations, with single locus mutation accounting for 96.85% and combined mutation accounting for 3.15%. The locus with the highest mutation rate was katG315 (71.65%). The proportion of base change in the form of AGC-ACC was the highest (12.13%). The proportion of mutations in katG, ahpC and kasA genes in INH-resistant strains was higher than that in susceptible strains (all P < 0.05). There was no significant difference in the proportion of mutations in inhA and fabG1 genes between INH-resistant strains and susceptible strains (all P>0.05). Beijing strains and non-Beijing strains had the highest mutation rates of katG315, which were 18.75% (81/432) and 4.55% (10/220) respectively. Difference in distribution of mutation loci of katG gene in two genotypes of strains was statistically significant(χ2=16.253, P=0.039). Conclusion The mutation of INH resistance gene in Guangxi region is mainly at katG315 locus, and the INH resistance phenotype and gene mutation are not consistent. Mutations in katG, ahpC and kasA genes are associated with INH phenotypic resistance. Beijing genotype is associated with the mutation of katG gene.

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秦翊翔,蓝如束,覃慧芳,等.广西地区结核分枝杆菌异烟肼耐药基因突变特征分析[J]. 中国感染控制杂志,2023,(3):280-286. DOI:10.12138/j. issn.1671-9638.20233443.
Yi-xiang QIN, Ru-shu LAN, Hui-fang QIN, et al. Mutation characterization of isoniazid resistance genes of Mycobacterium tuberculosis in Guangxi region[J]. Chin J Infect Control, 2023,(3):280-286. DOI:10.12138/j. issn.1671-9638.20233443.

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  • 收稿日期:2022-10-08
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  • 在线发布日期: 2024-04-28
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