四川地区结核分枝杆菌katG、inhA和rpoB基因突变位点耐药水平及突变频率特征分析  

Drug resistance and mutation frequency of katG, InhA and rpoB gene mutations in Mycobacterium tuberculosis in Sichuan province

作　　者：陈蕾 CHEN Lei(the Second Tuberculosis Area,Chengdu Public Health Clinical Medical Center,Chengdu,Sichuan 610000,China)

机构地区：[1]成都市公共卫生临床医疗中心(净居寺院区)结核二病区,四川成都610000

出　　处：《临床肺科杂志》2022年第2期242-246,共5页Journal of Clinical Pulmonary Medicine

摘　　要：目的分析基因芯片法(芯片法)检测结核分枝杆菌(Mtb)katG、inhA和rpoB基因突变位点耐药水平、突变频率特征,为临床治疗提供参考依据。方法选取成都市公共卫生临床医疗中心2020年1月—2021年1月收治的四川地区结核病患者118例Mtb分离株,芯片法通过katG、inhA和rpoB基因突变位点检测异烟肼(H)和利福平(R)耐药基因,微孔板比例法(比例法)通过培养+药物敏感性试验检测表型耐药水平,分析基因突变位点与耐药水平关系及突变频率分布特点。结果 H、R耐药株的耐药水平高,耐药相关基因的高耐药率为83.53%(71/85)、77.78%(77/99),基因突变位点与耐药水平关系密切,katG、inhA单基因突变位点的H高耐药率为92.96%(66/71)、30.77%(4/13),两者有统计学差异(χ^(2)=26.28 P<0.05)。rpoB单基因突变位点中rpoB531、rpoB526、rpoB533/516/513/511位点的R高耐药率为93.88%(49/49)、81.82%(18/22)、37.50%(9/24),三者有统计学差异(χ^(2)=29.17 P<0.05)。H耐药相关基因以katG315单基因突变为主,突变形式为(AGC→ACC) Ser→Thr(S315T),突变频率84.43%(71/85);R耐药相关基因以rpoB531单基因突变为主,突变形式为RRDR-531(TCG→TTG) Ser→Leu,突变频率49.50%(49/99)。结论四川地区H、R耐药株的耐药水平高。katG、rpoB531/526与H、R高耐药水平有关,inhA、rpoB511/513/516/533与H、R低耐药水平有关。katG315、rpoB531是H、R耐药相关基因突变的主要形式,临床使用抗结核药物须密切结合药敏检测制定方案。Objective To analyze the drug resistance level and mutation frequency of katG, InhA and rpoB gene mutations of Mycobacterium tuberculosis(MTB) by gene chip method, and to provide reference for clinical treatment.Methods 118 MTB isolates of tuberculosis patients from January 2020 to January 2021 in Chengdu public health clinical medical center were selected. Isoniazid(H) and rifampicin(R) resistance genes were detected by chip method using katG, InhA and rpoB gene mutation sites. The proportion method of microplate was used to detect the level of phenotypic drug resistance by culture and drug sensitivity test, and the relationship between gene mutation sites and drug resistance level and the distribution characteristics of mutation frequency were analyzed.Results The high drug resistance rates of H and R resistant strains were 83.53%(71/85) and 77.78%(77/99) respectively. There was a close relationship between gene mutation sites and drug resistance level. The H high resistance rates of katG and InhA single gene mutation sites were 92.96%(66/71) and 30.77%(4/13), respectively(χ^(2)=26.28, P<0.05). The R high resistance rates of rpob531, rpob526 and rpob533/516/513/511 were 93.88%(49/49), 81.82%(18/22) and 37.50%(9/24) in rpoB single gene mutation sites(χ^(2)=29.17, P<0.05). The mutation frequency of katg315 was 84.43%(71/85) in katg315 single gene, and rpob531(TCG → tTG) ser → Leu was the main mutation of R resistance related gene, and the mutation frequency was 49.50%(49/99).Conclusion The resistance level of H and R resistant strains is high in Sichuan. KatG and rpob531/526 are associated with high level of H and R resistance, InhA and rpob511/513/516/533 are associated with low level of H and R resistance. Katg315 and rpob531 are the main forms of H and R resistance related gene mutations. The clinical use of anti-tuberculosis drugs should be closely combined with drug sensitivity testing to develop a program.

关 键 词：结核分枝杆菌 基因芯片 耐药 比例法 

分 类 号：R446.5[医药卫生—诊断学] R52[医药卫生—临床医学]