基因芯片技术对耐多药结核病患者治疗的指导价值

Study on the value of genechip technology in the treatment of multidrug-resistant tuberculosis patients

目的:采用基因芯片技术检测耐药结核病菌株异烟肼耐药位点inh A-15(C-T)突变,为耐药结核病患者治疗提供指导。方法:从2014年1月1日~2016年12月31日,在江苏省连云港市结核病定点医院连续纳入涂阳结核病患者,利用基因芯片技术检测菌株利福平耐药相关基因rop B以及异烟肼耐药相关基因kat G和inh A的野生型及不同突变型。以传统药敏结果为金标准,分析异烟肼耐药相关位点inh A-15(C-T)的突变。结果:共有1 356例肺结核患者纳入最终结果分析,通过基因芯片技术检测1 356例患者痰涂片标本,22例(12.2%)仅出现了inh A位点突变不伴随kat G位点突变,其中耐多药结核病(multidrug-resistant tuberculosis,MDR-TB)3例占15.4%,早期广泛耐药结核(early extensive drug resistant tuberculosis,pre-XDR-TB)1例占7.7%,广泛耐药(extensively drug-resistant,XDR-TB)菌株3例占23.1%。有32例(17.7%)出现了inh A位点突变和(或)kat G位点突变,其中12例(23.1%)MDR-TB患者,3例(23.1%)为pre-XDR-TB患者,3例(23.1%)为XDR-TB患者。结论:超过10%耐药结核病患者的菌株出现了inh A-15位点的单突变,说明大剂量异烟肼可以用于治疗这些耐药患者。尽管乙(丙)硫异烟胺已经广泛应用于耐多药患者治疗中,但是近20%的耐药患者对其已经产生了耐药。基因芯片技术特异性报告耐药结核病患菌株的者位点突变,将对临床用药有一定的指导作用。

Objective：To detect the mutation of isoniazid resistance gene inh A-15（C-T）in drug-resistant tuberculosis strains by genechip technology,and to provide guidance for the treatment of drug-resistant tuberculosis patients. Method：From January 1,2014 to December 31,2016,patients with smear positive tuberculosis were continuously enrolled in TB designated hospitals in Lianyungang city of Jiangsu Province. The wild type and mutant type gene rpo B and wild type and mutant type of kat G and inh A were detected by gene chip technique. Based on the results of traditional susceptibility test,the mutation frequency of related resistance loci,especially the mutation of isoniazid resistance related gene inh A-15（C-T）,was analyzed in different drug-resistant strains. Results：A total of 1356 patients with pulmonary tuberculosis were included in the final analysis. Through the detection of genechip technology,22（12.2%）strains had a single mutation at inh A gene mutation without kat G mutation,Among them,3 cases of multidrug-resistant tuberculosis（MDR-TB）accounted for 15.4%,1 case of early extensive drug resistant tuberculosis（pre-XDR-TB）accounted for 7.7%,and 3 cases of extensively drug-resistant（XDR-TB）strains accounted for 23.1%. There were 32 cases（17.7%）had inh A gene mutation and/or kat G gene mutation,of which 12（23.1%）were in MDR-TB,3（23.1%）were in pre-XDR-TB,and 3（23.1%）were in XDR-TB.Conclusion：More than 10% drug-resistant TB patients have a single mutation at the inh A-15 locus,indicating that large doses of isoniazid can be used to treat these drug-resistant patients. Although ethionamide（protionamide）had been widely used in the treatment of MDR-TB patients,almost 20% of drug resistant patients were resistant to these two drugs. The application of genechip has specifically reported gene mutations in drug-resistant tuberculosis patients,which will have some guiding effect on clinical treatment.