结核分枝杆菌临床菌株katG、inhA和ahpC基因突变与异烟肼耐药的相关性研究  

Study on characteristics of katG,inhA and ahpC gene mutations in isoniazid resistant isolates of Mycobacterium tuberculosis

作　　者：蔡捷 刘小香[2] 李召东[3] 吴森林[2] 

机构地区：[1]浙江省药械采购中心,杭州310004 [2]浙江医学高等专科学校,杭州310053 [3]杭州市红十字会医院检验科,杭州311201

出　　处：《中国卫生检验杂志》2013年第6期1430-1432,共3页Chinese Journal of Health Laboratory Technology

基　　金：浙江医学高等专科学校博士基金项目(项目编号:2013B06)

摘　　要：目的:阐明结核分支杆菌耐异烟肼临床分离株katG、inhA和ahpC基因突变特点。方法:对75株耐异烟肼临床分离株和45株异烟肼敏感临床分离株katG、inhA和ahpC基因PCR并测序。结果:45株异烟肼敏感菌株中除18株katG基因存在R463L突变外无其它突变。75株耐异烟肼菌株中未发现katG、inhA和ahpC基因完全缺失。分别有68株、17株和8株分别发生katG、inhA和ahpC基因突变,43株(57.3%)发生katG基因S315位突变,结合菌株耐药程度,异烟肼高度耐药株(INH≥10μg/ml)S315突变发生率显著高于低度耐药株(INH≥1μg/ml)。33株(44%)katG基因存在R463L突变。结论:katG基因存在R463L突变同时存在于异烟肼敏感菌株和耐药菌株,无差异(P>0.05)提示katG基因R463L突变与异烟肼耐药无关,本地异烟肼耐药株katG基因突变特别是S315突变发生率高,S315突变与异烟肼耐药耐药密切相关且与耐药程度相关。Objective： To elucidate the characteristics of katG,inhA and ahpC gene mutations in isoniazid（INH） resistant isolates of Mycobacterium tuberculosis. Methods： A total of 75 INH - resistant isolates and 45 INH - susceptible isolates of Mycobacterium tuberculosis were analyzed by PCR and sequence analysis of their katG, inhA, and ahpC genes. Results： In addition to R463L mutation in katG gene was found in 18 INH - susceptible isolates, there was no other mutation in the 45 INH - susceptible isolates. Among the 75 INH - resistant isolates, complete deletions of katG, inhA and ahpC genes were not found, mutations in katG, inhA and ahpC were identified in 68, 17 and 8 isolates, respectively. S315 mutation were found in katG gene of 57.3% （43/75） of the INH - resistant isolates, high level INH- resistant isolates（ INH≥10ug/ml） had higher mutation frequency at S315 than low level INH - resistant isolates （ INH≥ 1ug/ml）. R463L was present in 33 of 75 INH - resistant isolates. Conclusions： R463 L mutation in katG gene was present in INH - susceptible and INH - resistant isolates, there was no statistically significant difference （P 〉 0.05）. It is suggested that the frequency of the S315 mutation in katG gene was high in the local isolates, S315 mutation was associated with high level INH -resistant isolates.

关 键 词：结核分枝杆菌 基因 突变 异烟肼 耐药 

分 类 号：R378.911[医药卫生—病原生物学]