结核病患者N-乙酰基转移酶2基因型与对氨基水杨酸异烟肼血药浓度关系分析

Relationship between N-acetyltransferase 2 genotype and concentration of Isoniazid aminosalicylate in the plasma of tuberculosis patients

目的:探讨结核病患者N-乙酰基转移酶2(NAT2)基因型与服用对氨基水杨酸异烟肼(PASINH)片后血浆中异烟肼(INH)浓度的相关性,为临床根据NAT2基因分型指导PAS-INH合理用药提供依据。方法:采用高效液相色谱法测定23例结核病患者服用PAS-INH片后2 h血浆中INH的浓度,同时提取血细胞基因组DNA,采用PCR-直接测序法(PCR-DS)测定结核病患者NAT2基因型。结果:23例结核病患者服用PAS-INH后2 h血浆中INH平均浓度为(1.35±1.17)mg·L-1。其中,NAT2快乙酰化基因型(RA)11例,血浆中INH平均浓度为(0.64±0.34)mg·L-1;中等乙酰化基因型(IA)7例,INH浓度为(1.40±0.87)mg·L-1;慢乙酰化基因型(SA)5例,INH浓度为(2.83±1.38)mg·L-1。RA患者与IA,SA患者的血浆INH浓度差异具有显著性意义(P值分别为0.021,0.002,P<0.05)。结论:NAT2 SA和IA基因型结核病患者血浆中INH浓度显著高于RA基因型患者,NAT2基因型分析可能对结核病患者PAS-INH合理用药具有重要指导意义。

Objective： To investigate the correlation between N-acetyltransferase 2 （NAT2） genotype and concentrations of isoniazid （INH） in the plasma of tuberculosis （TB） patients 2 h after taking isoniazid aminosalicylate tablets （PAS-INH） , so as to provide a basis for the guidance of rational use of PAS-INH by NAT2 genotyping. Methods： The concentration of INH in the plasma from 23 TB patients was determined by a high-perform- ance liquid chromatography （HPLC） 2 h after taking PAS-INH. The genomic DNAs of blood cells were extracted, and then NAT2 genotypes were analyzed by PCR-direct sequencing （PCR-DS）. Results： The average plasma concentration of INH in the 23 TB patients was （ 1.35 ± 1.17） mg. L-I Of 23 TB patients, 11 were rapid acetylation （RA） genotype and their average concentration of INH in plasma was （0.64 ＋- 0.34） mg·L^-1; 11 were intermediate acetylation （IA） genotype and their INH concentration was （ 1.40 ± 0.87） ·L^-1 ; 5 were slow acetylation （SA） genotype and their INH concentration was （2.83 ± 1.38） mg·L^-1 The plasma INH concentration in the patients with RA-type significantly differed from those in patients with IA- and SA-type （P = 0. 021 for RA vs IA, P = 0. 002 for RA vs SA, P 〈 0.05 ; but P = 0. 062 for IA vs SA, P 〉 0.05）. Conclusion： The plasma INH concentration in patients with NAT2 SA- and IA-genotype is significantly higher than that in patients with RA-genotype. NAT2 genotyping may have important guiding significance for rational use of PAS-INH in the TB patients