肺结核患者标准治疗过程中GSTs基因多态性与抗结核药物血药浓度相关性研究  

The relationship between GSTs gene polymorphism and the concentration of anti-tuberculosis drugs in tuberculosis patients during the standard treatment

作　　者：张敏[1] 李星星 何霞[2,3] 袁丽 程希[1] 童荣生[2,3] ZHANG Min;LI Xing-xing;HE Xia;YUAN Li;CHENG Xi;TONG Rong-sheng(Department of Pharmacy,The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610071,China;Department of Pharmacy,Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital,Chengdu 610072,China;Personalized Drug Therapy Key Laboratory of Sichuan Province,School of Medicine,University of Electronic Science and Technology of China,Chengdu 610072,China)

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

出　　处：《实用医院临床杂志》2021年第4期50-53,共4页Practical Journal of Clinical Medicine

基　　金：四川省科技计划基金资助项目(编号2019YJ0575);四川省卫生与健康委员会普及应用项目(编号18PJ544)。

摘　　要：目的研究肺结核患者的GSTs(rs1045642)基因多态性与结核标准治疗方案治疗后血浆中抗结核药物血药浓度的相关性。方法采用前瞻性研究的方法纳入2019年1月至2020年12月在成都中医学院附属医院和四川省人民医院诊断为肺结核的60名住院治疗患者。在接受抗结核治疗前应用聚合酶链反应(PCR)-芯片杂交技术测定GSTs基因GSTM1、GSTT1、GSTP1的基因型。抗结核治疗开始后7天采集患者外周血,应用超高效液相色谱串联质谱法测定血浆中抗结核药物浓度。结果GSTM1、GSTT1基因的突变组与未突变组之间以及GSTP1基因AA组、AG组、GG组三组之间异烟肼、利福平、吡嗪酰胺血药浓度相比较,差异无统计学意义(P>0.05)。吡嗪酰胺血药浓度中位数值GSTP1 AG+GG组6.032(7.360)μmol/ml,GSTP1 AA组11.74(21.170)μmol/ml,两组间比较差异有统计学意义(P<0.05)。结论GSTM1、GSTT1和GSTP1的基因多态性不影响异烟肼、利福平的血药浓度;GSTP1的基因多态性与吡嗪酰胺的血药浓度具有相关性。Objective To investigate the relationship between GSTs(rs1045642)gene polymorphism and plasma concentration of anti-tuberculosis drugs of tuberculosis patients during the standard treatment.Methods A prospective study was conducted on 60 hospitalized patients with pulmonary tuberculosis diagnosed in our hospitals from January 2019 to December 2020.The genotypes of GSTs genes GSTM1,GSTT1,and GSTP1 were determined by using polymerase chain reaction(PCR)-microarray hybridization before anti-tuberculosis treatment.The blood samples were collected after 7 days of anti-tuberculosis treatment.The concentration of anti-tuberculosis drugs in plasma was determined by using ultra performance liquid chromatography-MS/MS(UPLC-MS/MS).Results There was no significant difference in plasma concentrations of isoniazid,rifampicin and pyrazinamide between the group with GSTM1 and GSTT1 mutations and the wildtype group,neither were significant differences among GSTP1 AA group,AG group and GG group(P>0.05).The median plasma concentration of pyrazinamide was 6.032(7.360)μmol/ml in GSTP1 AG+GG group and 11.74(21.170)μmol/ml in GSTP1 AA group,and there was a significant difference between the two groups(P<0.05).Conclusion GSTM1,GSTT1 and GSTP1 gene polymorphisms do not affect the plasma concentrations of isoniazid and rifampicin.GSTP1 gene polymorphisms are correlated with the plasma concentrations of pyrazinamide.

关 键 词：肺结核 GSTS 基因多态性 血药浓度 

分 类 号：R9[医药卫生—药学] R52