【摘要】 目的 研究经结核标准治疗方案治疗后肺结核患者抗结核药物血药浓度与其NAT2基因多态性间的相关性。方法 纳入2019年1月至2021年6月于四川省人民医院和成都中医药大学附属医院诊断为肺结核的住院患者55例为研究对象。未接受治疗前，采用荧光定量PCR探针法测定患者NAT2基因的基因型。抗结核治疗后7 d,应用超高效液相色谱串联质谱法测定患者的抗结核药物血药浓度。根据乙酰化能力不同，将患者分为快乙酰化型(RA)组19例、中乙酰化型(IA)组29例和慢乙酰化型(SA)组7例。结果 NAT2基因SA组吡嗪酰胺、异烟肼和利福平的血药浓度分别为6.61(4.84,26.80)、0.25(0.25,0.85)、0.25(0.25,1.17)mg/L。Spearman相关分析显示，各组NAT2基因型与吡嗪酰胺、利福平、异烟肼血药浓度间无相关性(P>0.05);RA组、IA组和SA组与吡嗪酰胺、利福平及异烟肼血药浓度间无相关性(P>0.05)。结论 肺结核患者标准治疗过程中，NAT2基因多态性不是吡嗪酰胺、异烟肼和利福平血药浓度的主要影响因素。更多还原

【Abstract】 Objective To study the correlation between N-acetyltransferase 2(NAT2) gene polymorphism and plasma concentration of anti-tuberculosis drugs in tuberculosis patients undergoing standard treatment. Methods A total of 55 inpatients diagnosed with tuberculosis in Sichuan Provincial People′s Hospital and the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2019 to June 2021 were included in this study. The genotypes of NAT2 genes were determined by fluorescence quantitative polymerase chain reaction probe before anti-tuberculosis treatment. Plasma concentrations of anti-tuberculosis drugs were determined by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) 7 days after the initiation of anti-tuberculosis therapy. According to the difference of acetylation ability, the patients were divided into rapid acetylator group(RA group, n=19), intermediate acetylator group(IA group, n=29), and slow acetylator group(SA group, n=7). Results The plasma concentrations of pyrazinamide(PZA), isoniazid(INH) and rifampicin(RFP) of NAT2 gene SA group were 6.61(4.84, 26.80)mg/L, 0.25(0.25, 0.85)mg/L and 0.25(0.25, 1.17)mg/L, respectively. Spearman correlation analysis showed that there was no correlation between NAT2 genotypes and plasma concentrations of PZA, RFP and INH in each group(P>0.05). There was no correlation between RA group, IA group and SA group and the plasma concentrations of PZA, RFP and INH(P>0.05). Conclusion NAT2 gene polymorphism is not a major factor influencing the plasma concentrations of PZA, RFP and INH in tuberculosis patients undergoing standard treatment.更多还原