【摘要】 目的探讨结核病患者N-乙酰基转移酶2(NAT2)基因型与异烟肼(INH)血药浓度的关联性,为临床根据NAT2基因分型指导合理INH用药提供依据。方法应用PCR结合限制性片段长度多态性(PCR-RFLP)方法对121例住院结核病患者NAT2基因型分布进行检测,同时应用液相色谱-串联质谱分析仪(LC/MS-MS)检测结核病患者服药2h后血浆INH浓度。所获数据采用单因素方差分析检测组间差异,进而采用Tamhane’s T2法进行两两比较,以P<0.05为差异有统计学意义。结果 121例结核病患者NAT2基因型中快速乙酰化型(RA,野生型)有55例,INH血药浓度为(1.86±1.28)μg/ml;慢乙酰化型(SA,纯合突变型)有17例,INH血药浓度为(5.86±2.10)μg/ml;中间乙酰化型(IA,杂合突变型)有49例,INH血药浓度(3.49±2.60)μg/ml。住院结核病患者整体INH血药浓度均值为(3.08±2.42)μg/ml。三型INH血药浓度比较,差异均具有显著统计学意义(RA与IA,P=0.001;RA与SA,P=0.002;IA与SA,P=0.000)。结论不同NAT2基因型人群对INH的代谢能力差异存在显著统计学意义,NAT2基因型分析对结核病患者INH用药具有重要指导意义。更多还原

【Abstract】 Objective To study the correlation between N-acetyltransferase 2(NAT2) genotypes and the concentration of isoniazid(INH) in the plasma,and provide a theoretical basis for the individualized medication of tuberculosis(TB) patients by NAT2 genotyping.Methods The NAT2 genotypes of 121 TB patients were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).INH concentration in the plasma was detected by the liquid chromatography-tandem mass spectrometry(LC/MS-MS) at 2 hours after treatment.The differences between the groups were tested by using single factor analysis of variance,and then the differences of every two groups were tested by using Tamhane’s T2,P<0.05 was considered statistically significant.Results Of 121 TB patients,55 were NAT2 rapid acetylation(RA) type,and their average concentration of INH in plasma was(1.86±1.28)μg/ml;17 were slow acetylation(SA) type(homozygous mutant),their INH concentration was(5.86±2.10)μg/ml;49 were intermediate acetylation(IA) type(heterozygous mutant),and the INH concentration was(3.49±2.60)μg/ml.INH concentration of hospitalized TB patients in plasma was(3.08 ± 2.42)μg/ml.INH concentration among the three groups have statistically significant differences(RA with IA,P=0.001;RA with SA,P=0.002;IA with SA,P=0.000,P<0.05).Conclusion There were significant differences among the TB patients with different NAT2 genotypes.NAT2 genotyping has important guiding significance for the INH treatment in the TB patients.更多还原