细胞色素P450—2E1基因多态性与抗结核药物性肝损害的相关性  

Association of P450-2E1 and GSTM1 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity

作　　者：王涛 王巍 王仲元 潘燕玉[2] 苏琼琼 贺路星 

机构地区：[1]解放军第三〇九医院全军结核病研究所,北京100091 [2]解放军福州总医院结核科

出　　处：《中华结核和呼吸杂志》2009年第8期585-587,共3页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的分析细胞色素P450-2E1基因多态性与抗结核药物性肝损害的相关性，探讨抗结核药物性肝损害的遗传基础及易患因素。方法收集解放军总医院第二附属医院结核病研究所85例（男52例，女33例，年龄18—70岁），抗结核药物性肝损害患者（肝损害组）及该院同期抗结核治疗无肝损害者100例（男64例，女36例，年龄18—75岁，对照组）外周血液标本，采用PCR-限制性片段长度多态性分析测定P450-2E1 Rsa I 各基因型的分布频率。两组等位基因分布频率的差异采用χ^2检验，采用logistic回归分析抗结核药物性肝损害的易感因素。结果肝损害组P450—2ElRsaIel／el、cl／c2和c2／c2基因型分布频率分别为75％（64／85）、20％（17／85）和5％（4／85），与对照组的61％（61／100）、30％（30／100）和9％（9／100）比较，cl／cl频率显著增高（）（。：4．284，P〈0．05，OR=1．948，95％a为1．032—3．680），logistic回归分析结果提示，性别、年龄、体重指数等因素与抗结核药物性肝损害无关，cl／cl基因型是抗结核药物性肝损害独立危险因素（OR=2．016，95％CI为1．058—3．842）。结论P450-2E1基因多态性与抗结核药物性肝损害显著相关，el／c1野生基因型是引起抗结核药物性肝损害的易患因素之一。Objective To observe the relationship between the genetic polymorphism of P450-2E1 and the risk for antituberculosis drug-induced hepatotoxicity in a Chinese population. Methods Blood samples and clinical data were collected from 85 patients with antituberculosis drug-induced hepatotoxicity and 100 tuberculosis patients without hepatotoxicity as the control. DNA was extracted from the blood samples, and the frequencies of P450-2E1 Rsa I genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. The relationship between the polymorphisms of P450-2E1 Rsa I and the antituberculosis drug-induced hepatotoxicity was analyzed. Predisposing factors for antituberculosis drug-induced hepatitis, such as gender, age, and polymorphism of P450-2E1 Rsa I were evaluated by using logistic regression analysis. Results The frequencies of the 3 gene types P450-2E1 Rsa I c1/c1, c1/c2, and c2/c2 were 75% （64/85）, 20% （17/85） and 5% （4/85） respectively in patients with antituberculosis drug-induced hepatotoxicity, and 61% （61/100）, 30% （30/100）, and 9% （9/100）respectively in the controls. A statistical difference was found between the cases and the controls （χ^2 = 4. 284,P 〈 0. 05, OR = 2. 016, 95% CI = 1. 058 - 3. 842）. Logistic regression analysis showed that the polymorphism of P450-2E1 Rsa I remained a significant independent risk faetor for antitubereulosis drug- induced hepatotoxicity after adjustment for age, gender and body mass index. Conclusion Polymorphisms of P450-2E1 were found to he significantly associated with the risk of antitubereulosis drug-induced hepatotoxicity, and the el/el genotype was one of the risk factors.

关 键 词：细胞色素P450 CYP2E1 基因 多态性 限制性片段长度 抗结核药 肝炎 中毒性 

分 类 号：R686[医药卫生—骨科学]