Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil
Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil
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DOI：
10.1007/s00228-008-0484-8
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发表时间：
2008-07-01
影响因子：
2.9
通讯作者：
Zaha, A.
中科院分区：
文献类型：
--
作者：
Possuelo, L. G.;Castelan, J. A.;Zaha, A.
目的确定巴西人群中N-乙酰转移酶2（NAT 2）多态性频率、NAT 2乙酰化谱及其与胃肠道药物不良反应（ADR）发生率、抗结核（TB）药物诱导的肝毒性和肝毒性临床危险因素的关系。和吡嗪酰胺（PZA）在一项前瞻性队列研究中进行了测试。通过直接PCR测序进行NAT 2基因分型。结果254例患者中，69例（27.2%）为慢乙酰化者，185例（72.8%）为快乙酰化者。65例（25.6%）患者为人类免疫缺陷病毒（HIV）阳性。分别有33例（13%）和14例（5.5%）患者发生胃肠道ADR和肝毒性。在14例肝毒性患者中，9例（64.3%）为慢乙酰化者，5例（35.7%）为快乙酰化者。未发现性别、年龄、丙型肝炎病毒、酗酒和基线转氨酶是肝毒性的危险因素。然而，逻辑回归分析显示，慢乙酰化状态和存在的HIV（p < 0.05）是独立的危险因素肝toxicity.Conclusions我们的研究结果表明，HIV阳性患者，具有慢乙酰化配置文件是显着相关的抗结核药物肝毒性的风险较高。
Purpose To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil.Methods Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression.Results Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity.Conclusions Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs.