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首页> 外文期刊>The Journal of toxicological sciences >Effects of N-acetyltransferase 2 (NAT2), CYP2E1 andGlutathione-S-transferase (GST) genotypes on the serumconcentrations of isoniazid and metabolites in tuberculosispatients
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Effects of N-acetyltransferase 2 (NAT2), CYP2E1 andGlutathione-S-transferase (GST) genotypes on the serumconcentrations of isoniazid and metabolites in tuberculosispatients

机译：N-乙酰基转移酶2（NAT2），CYP2E1和谷胱甘肽-S-转移酶（GST）基因型对结核病患者异烟肼和代谢物血清浓度的影响

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摘要

For the purpose of a side-effect monitoring of isoniazid (INH), we investigated the relationship between the genotypes of drug-metabolizing enzymes involved in INH metabolism and the serum concentrations of INH and its metabolites in 129 tuberculosis patients hospitalizing in the National Hospital Organization Chiba-East Hospital. Genotype distributions of N-acetyltransferase 2 (NAT2), CYP2E1*5B, CYP2E1*6, Glutathione-S-transferase (GST) Ml and GST Tl were similar to those already reported in Japanese populations. Acetylating pathway of INH to acetyl isoniazid (AcINH) tended to shift to the hydro lytic pathway generating hydrazine (Hz) with the increase of mutant alleles in NAT2 gene. Serum concentration of Hz was significantly higher in slow acetylators than in rapid acetylators of NAT2. And also, serum concentration of Hz was significantly higher in the group that showed a high concentration of rifampicin (RFP) than in which RFP was not detected. The effect of CYP2E1 gene polymorphisms on the serum concentration of Hz was rarely observed, while that of GST gene polymorphism was observed in intermediate acetylators of NAT2. Hz tended to accumulate in patients with GST Ml null genotype. Therefore, it is conceivable that the risk factors of Hz accumulation are as follows: NAT2 slow acetylator phenotype, high concentration of serum RFP, and GST Ml null genotype. In these cases, we think it's necessary to pay attention to the development of hepatic disorder caused by Hz.
机译：为了对异烟肼（INH）进行副作用监测，我们调查了在美国国家医院组织住院的129名肺结核患者中，涉及INH代谢的药物代谢酶的基因型与INH及其代谢产物的血清浓度之间的关系千叶东医院。 N-乙酰基转移酶2（NAT2），CYP2E1 * 5B，CYP2E1 * 6，谷胱甘肽-S-转移酶（GST）M1和GST T1的基因型分布与日本人群中已经报道的相似。随着NAT2基因突变等位基因的增加，INH向乙酰基异烟肼（AcINH）的乙酰化途径倾向于转移至生成肼（Hz）的水解途径。慢乙酰化剂的血清Hz浓度显着高于NAT2快乙酰化剂。而且，显示出高浓度利福平（RFP）的组中的Hz血清浓度显着高于未检测到RFP的组。很少观察到CYP2E1基因多态性对血清Hz的影响，而在NAT2的中间乙酰化剂中观察到GST基因多态性的影响。在具有GST M1无效基因型的患者中，Hz倾向于积累。因此，可以想象的是，Hz积累的危险因素如下：NAT2慢乙酰化表型，高浓度血清RFP和GST M1无效基因型。在这种情况下，我们认为有必要注意由Hz引起的肝病的发展。

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