Genotype and phenotype of NAT2 and the occurrence of adverse drug reactions in Mexican individuals to an isoniazid-based prophylactic chemotherapy for tuberculosis
Genotype and phenotype of NAT2 and the occurrence of adverse drug reactions in Mexican individuals to an isoniazid-based prophylactic chemotherapy for tuberculosis
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DOI：
10.3892/mmr_00000044
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Soria-Rodriguez, Carmen G.
中科院分区：
文献类型：
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作者：
Diaz-Molina, Raul;Cornejo-Bravo, Jose M.;Soria-Rodriguez, Carmen G.
异烟肼(INH)是一种广泛用于人类结核病(TB)预防和治疗的药物。INH的代谢是通过N-乙酰转移酶2(NAT2)的酶活性来实现的。人类NAT2由一个高度多态的基因编码，参与了外源物质的生物转化，包括药物和某些化学致癌物。许多研究已经确定了在几个人群中乙酰化表型和Nat2基因之间的相关性；然而，关于拉丁美洲人群和Nat2的药物遗传学知之甚少。在这里，我们报告了一组参加结核病预防方案的25名墨西哥人的NAT2基因的分子基因分型、乙酰化表型和异烟肼相关不良反应的发生率。同时使用Nat2基因分型和乙酰化表型方法，我们发现慢乙酰化和快乙酰化的比例分别为69.2%和30.8%。在双峰模型中，Nat2基因分型与表型分类的符合率为88%。关于异烟肼相关的不良反应，只有2人(8%)表现出明显的胃不耐受。在我们的研究组中，我们发现NAT2基因与乙酰化表型之间存在关联(OR=7.78，95%CI，0.87-87.98，Fisher‘s Exact检验，p
Isoniazid (INH) is a drug extensively used as a prophylactic and therapeutic agent for human tuberculosis (TB). INH is metabolized by the enzymatic activity of N-acetyltransferase 2 (NAT2). Human NAT2, encoded by a highly polymorphic gene, is involved in the biotransformation of xenobiotics, including drugs and certain chemical carcinogens. Numerous studies have established the correlation between the acetylator phenotype and the NAT2 genotype in several populations; however, little is known regarding Latin-American populations and the pharmacogenetics of NAT2. Here, we report the molecular genotyping of the NAT2 gene, the acetylator phenotype, and the incidence of INH-related adverse reactions in a group of 25 Mexican individuals enrolled in a prophylactic protocol for TB. Using both the NAT2 genotyping and acetylation phenotyping approach, we found a ratio of 69.2 and 30.8% of slow and fast acetylators, respectively. Concordance of the NAT2 genotype and phenotype classification was 88% in the bimodal model. Regarding INH-related adverse reactions, only 2 individuals (8%) exhibited declared gastric intolerance. In our study group, we found an association between the NAT2 genotype and acetylator phenotype (OR=7.78, 95% CI, 0.87-87.98, Fisher's exact test, p