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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 investigate the association between N-acetyltransferase 2 (NAT2) genotypes and the plasma concentration of isoniazid (INH) in tuberculosis patients, and to provide a basis for clinical use of NAT2 genotyping to guide rational use of INH. Methods The distribution of NAT2 genotypes in 121 hospitalized tuberculosis patients was detected by PCR and restriction fragment length polymorphism (PCR-RFLP). Meanwhile, LC-MS / MS was used to detect the distribution of NAT2 genotype in hospitalized patients with tuberculosis. After 2h plasma INH concentration. The data obtained using single-factor analysis of variance to detect differences between groups, and then use the method of Tamhane’s T2 for any comparison, P <0.05 was considered statistically significant. Results There were 55 cases of NAT2 genotypes in NAT (n = 26) and INH (1.86 ± 1.28) μg / ml in the 121 cases of NAT. The slow acetylated (SA, homozygous mutant) In 17 cases, the INH plasma concentration was (5.86 ± 2.10) μg / ml; 49 cases were intermediate acetylated (IA, heterozygous mutant) and INH plasma concentration was 3.49 ± 2.60 μg / ml. Inpatients with tuberculosis overall INH blood concentration mean (3.08 ± 2.42) μg / ml. There was significant difference between the three types of INH blood concentration (RA and IA, P = 0.001; RA and SA, P = 0.002; IA and SA, P = 0.000). CONCLUSION: There are significant differences in the metabolic capacities of INH between different NAT2 genotypes, and NAT2 genotype analysis is of great guiding significance for INH drug use in tuberculosis patients.