结核病患者N-乙酰基转移酶2基因型与异烟肼血药浓度关系的研究

The relationship between N-acetyltransferase 2 genotypes and the concentration of isoniazid in human plasma

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。

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 ana- lyzed 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 signifi- cant. 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 con- centration 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.