Sistanizad Mohammad, Azizi Ebrahim, Khalili Hosein, Hajiabdolbaghi Mahboobeh, Gholami Kheirollah, Mahjub Reza
Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2011 Summer;10(3):633-9.
The aim of this study was to determine the association of n-acetyltransferase-2 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Iranian pulmonary tuberculosis patients. Acetylating phenotypes was studied in 50 Iranian pulmonary tuberculosis patients using metabolic ratio of plasma acetyl-Isoniazid to Isoniazid. The association between hepatotoxicity and the n-acetyltransferase-2 phenotype was evaluated by using the chi-square (x(2)) test. The metabolic ratio had a bimodal distribution with an antimode value of 1.0. Based on the metabolic ratio of the mentioned patients, 20 (40%) were slow acetylators and 30 (60%) were fast ones. Hepatotoxicity was manifested in 9 of 20 slow acetylators (45%) and only in 5 of 30 rapid acetylators (16.7%). There was a significant difference in the frequency of hepatotoxicity between the slow and fast acetylators (x(2) = 4.778, and p = 0.03). Sex and age were not found to be risk factors for hepatotoxicity. Our findings show that slow acetylation profile is significantly associated with a higher risk of developing hepatotoxicity due to the anti-TB drugs in Iranian pulmonary tuberculosis patients.
本研究的目的是确定伊朗肺结核患者中N-乙酰转移酶-2基因多态性与抗结核药物所致肝毒性之间的关联。采用血浆乙酰异烟肼与异烟肼的代谢比值，对50例伊朗肺结核患者的乙酰化表型进行了研究。使用卡方（x²）检验评估肝毒性与N-乙酰转移酶-2表型之间的关联。代谢比值呈双峰分布，反众数为1.0。根据上述患者的代谢比值，20例（40%）为慢乙酰化者，30例（60%）为快乙酰化者。20例慢乙酰化者中有9例（45%）出现肝毒性，而30例快乙酰化者中仅有5例（16.7%）出现肝毒性。慢乙酰化者和快乙酰化者肝毒性的发生率存在显著差异（x² = 4.778，p = 0.03）。未发现性别和年龄是肝毒性的危险因素。我们的研究结果表明，在伊朗肺结核患者中，慢乙酰化表型与抗结核药物所致肝毒性的较高风险显著相关。
