Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity.
Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin-induced hepatotoxicity.
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发表时间：
2000-03
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通讯作者：
M. Ohno;I. Yamaguchi;I. Yamamoto;Tomiko Fukuda;S. Yokota;R. Maekura;M. Ito;Y. Yamamoto;T. Ogura;K. Maeda;K. Komuta;T. Igarashi;J. Azuma
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作者：
M. Ohno;I. Yamaguchi;I. Yamamoto;Tomiko Fukuda;S. Yokota;R. Maekura;M. Ito;Y. Yamamoto;T. Ogura;K. Maeda;K. Komuta;T. Igarashi;J. Azuma
日本住院肺结核患者，肝功能正常，接受异烟肼和利福平（INH + RMP）治疗。目的探讨N-乙酰基转移酶2（NAT 2）基因型与异烟肼+利福平肝毒性发生率的关系。设计前瞻性研究。经NAT 2 * 基因分型后，将77例患者根据其NAT 2 * 基因型分为3组：快速型（NAT 2 *4纯合子）、中间型（NAT 2 *4杂合子和突变等位基因）和慢速型（突变等位基因的组合）。对他们的肝功能生化检查进行了为期3个月的研究，以评估血清转氨酶升高的发展情况。结果在77例患者中，18.2%的患者在INH + RMP治疗的第一个月内发生了不良肝脏反应。肝毒性与NAT 2 * 基因型显著相关：与快速型相比，中间型的相对危险度为4.0（95%CI 1.94-6.06），缓慢型为28.0（95%CI 26.0-30.0）。尤其是慢型，肝毒性和血清转氨酶升高的发生率明显高于其他两种类型。结论慢NAT 2 * 基因型对INH + RMP肝毒性的发生有显著影响。这表明用药前NAT 2 * 基因分型可能有助于评估INH + RMP诱导的肝毒性高风险患者。
SETTING Japanese in-patients with pulmonary tuberculosis and normal liver function receiving treatment with isoniazid and rifampicin (INH + RMP). OBJECTIVE To elucidate the relationship between N-acetyltransferase 2 (NAT2) genotype and the incidence of isoniazid + rifampicin-induced hepatotoxicity. DESIGN Prospective study. After NAT2* genotyping, 77 patients were classified into three groups according to their NAT2* genotypes: rapid-type (a homozygote of NAT2*4), intermediate-type (a heterozygote of NAT2*4 and mutant alleles) and slow-type (a combination of mutant alleles). Their biochemical profiles of liver function test were investigated for 3 months to assess the development of serum aminotransferase elevation. RESULT Of the 77 patients, 18.2% developed adverse hepatic reaction within the first month of INH + RMP treatment. A significant association was observed between hepatotoxicity and NAT2* genotype: compared with rapid-type, the relative risk was 4.0 (95% CI 1.94-6.06) for intermediate-type and 28.0 (95%CI 26.0-30.0) for slow-type. Especially in slow-type, the incidence of hepatotoxicity and serum aminotransferase elevation was significantly higher than in the other two types. CONCLUSION Slow NAT2* genotype significantly affected the development of INH + RMP-induced hepatotoxicity. This suggests the possibility that NAT2* genotyping prior to medication may be useful in evaluating patients with high risk for INH + RMP-induced hepatotoxicity.