合肥地区异烟肼耐药结核分枝杆菌KatG基因突变的分子特征

发布时间：2018-06-27 17:46

本文选题：结核分枝杆菌 + 异烟肼耐药　；参考：《现代预防医学》2013年06期

【摘要】：目的了解合肥地区结核分枝杆菌异烟肼(Isoniazid,INH)耐药株katG基因突变特点。方法应用PCR-直接测序法对合肥地区肺结核病人痰液中分离的86株结核分枝杆菌的katG基因731bp序列进行测定分析。结果 86株结核分枝杆菌中67株对INH耐药,19株对INH敏感;67株耐INH临床分离株中PCR成功扩增61株,其中56株发生katG基因突变,突变率为91.8%(56/61);katG基因发生联合突变的有30株,突变率为49.2%(30/61),26株发生katG基因单位点突变,突变率为42.6%(26/61)。突变位点主要集中在463位精氨酸和315位丝氨酸,突变率分别为93.4%(57/61)和42.6%(26/61)。而在19株INH敏感株中发现有78.9%(15/19)株存在Arg4631eu突变,突变形式与INH耐药株相同。结论在合肥地区,KatG基因315位密码子突变是菌株INH表型耐药的重要分子基础,以Ser315Thr错义突变为主。KatG基因463位密码子突变与INH耐药表型没有相关性,不是结核杆菌INH耐药的分子标志。该位点突变可能是基因多态性,与结核茵治疗带来的选择性压力无关。
[Abstract]:Objective to investigate the characteristics of katG gene mutation in isoniazidazid INH resistant strains of Mycobacterium tuberculosis in Hefei. Methods the katG gene 731bp sequences of 86 strains of Mycobacterium tuberculosis isolated from sputum of pulmonary tuberculosis patients in Hefei were determined by PCR- direct sequencing. Results among the 86 strains of Mycobacterium tuberculosis, 67 strains were resistant to INH and 19 strains were susceptible to INH. Among them, 61 strains were successfully amplified by PCR. Among them, 56 strains had katG gene mutation, the mutation rate was 91.8% (56 / 61) and the co-mutation of katG gene was found in 30 strains. The mutation rate was 49.2% (30 / 61) and the mutation rate was 42.6% (26 / 61). The mutation sites were mainly arginine at 463 and serine at 315 with mutation rates of 93.4% (57 / 61) and 42.6% (26 / 61), respectively. Arg4631eu mutation was found in 78.9% (15 / 19) of the 19 INH-sensitive strains, and the mutation pattern was the same as that of the INH-resistant strains. Conclusion the 315 codon mutation of KatG gene in Hefei is an important molecular basis for phenotype resistance of INH. The codon 463 mutation of the Ser315Thr missense mutation has no correlation with the phenotype of INH resistance. It is not a molecular marker for INH resistance of Mycobacterium tuberculosis. This locus mutation may be a genetic polymorphism, independent of the selective stress associated with TB therapy.
【作者单位】：合肥市疾病预防控制中心;安徽省肺科医院检验科;
【分类号】：R378.911

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