Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis
Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis
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DOI：
10.1053/jhep.2002.32102
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发表时间：
2002-04-01
期刊：
影响因子：
13.5
通讯作者：
Lee, SD
中科院分区：
文献类型：
--
作者：
Huang, YS;Chern, HD;Lee, SD
抗结核药物性肝炎是最常见的药物性肝损伤之一。异烟肼是导致这种肝毒性的主要药物。异烟肼主要代谢为肝毒性中间体！N-乙酰转移酶（NAT）。然而，多态性NAT乙酰化状态与抗结核药物诱导的肝炎之间的关联是有争议的。为了确定乙酰化状态是否是抗结核药物性肝炎的危险因素，我们对224例接受抗结核治疗的结核病患者进行了NAT 2基因分型。根据异烟肼再激发试验阳性和排除病毒性肝炎，诊断为抗结核药物诱导的肝炎。乙酰化状态通过使用限制性片段长度多态性聚合酶链反应对患者进行NAT 2基因分型来确定。采用单因素分析和Logistic回归分析异烟肼致肝炎的危险因素。抗结核药物性肝炎33例（14.7%）。慢乙酰化者的肝毒性风险高于快乙酰化者（26.4% vs. 11.1%，P = 0.013）。在肝毒性患者中，缓慢乙酰化！Logistic回归分析显示，慢乙酰化状态（OR，3.66; 95%CI，1.58-8.49; P = 0.003）和年龄（OR，1.09; 95%CI，1.04-1.14; P = 0.003）与慢性乙酰化状态（OR，3.66; 95%CI，1.58- 8.49; P = 0.003）有关。
Antituberculosis drug-induced hepatitis, is ones of the most prevalent drug-induced liver injuries. Isoniazid is the major drug incriminated in this hepatotoxicity. Isoniazid is mainly metabolized to hepatotoxic intermediates! by N-acetyltransferase (NAT). However, the association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is debatable. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2 in 224 incident tuberculosis patients who received antituberculosis treatment. Antituberculosis drug-induced hepatitis was diagnosed based on a positive isoniazid rechallenge test and exclusion of viral hepatitis. Acetylator status was determined by genotyping NAT2 in patients using a polymerase chain reaction with restriction fragment length polymorphism. Univariate analysis, and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. Thirty-three patients (14.7%) were diagnosed with antituberculosis drug-induced hepatitis. Slow acetylators had a higher risk of hepatotoxicity than rapid acetylators (26.4% vs. 11.1%, P =.013). Among patients with hepatotoxicity, slow acetylators! had significantly higher serum aminotransferase levels than rapid acetylators; Logistic regression showed that slow-acetylator status (odds ratio [OR], 3.66; 95% Cl, 1.58-8.49; P =.003) and age (OR, 1.09; 95% Cl, 1.04-1.14; P