NAT2基因多态性与抗结核药物血药浓度相关性分析  

Analysis of the Relationship Between N-acetyltransferase 2 Gene Polymorphism and Plasma Concentration of Anti-tuberculosis Drugs

作　　者：张敏[1,2,4] 徐娜[1,2] 李星星 张雪 何霞 Zhang Min;Xu Na;Li Xingxing;Zhang Xue;He Xia(Department of Pharmacy, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610071, China;School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China;Department of Pharmacy, Sichuan Provincial Academy of Medical Sciences·Sichuan Provincial People′s Hospital, Chengdu 610072, China;School of Medicine, University of Electronic Science and Technology of China·Key Laboratory of Personalized Medicine of Sichuan Province, Chengdu 610072, China)

机构地区：[1]成都中医药大学附属医院药剂科,成都610071 [2]成都中医药大学药学院,成都611137 [3]四川省医学科学院·四川省人民医院药学部,成都610072 [4]电子科技大学医学院·个体化药物治疗四川省重点实验室,成都610072

出　　处：《成都医学院学报》2022年第3期311-315,共5页Journal of Chengdu Medical College

基　　金：四川省科技厅科技计划基金资助项目(No:2019YJ0575);四川省卫生与健康委员会普及应用项目(No:18PJ544)。

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。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.

关 键 词：肺结核 NAT2 基因多态性 血药浓度 

分 类 号：R521[医药卫生—内科学] R969.1[医药卫生—临床医学]