CYP2E1和NAT2基因多态性与抗结核药物诱导的药物性肝损伤关系的荟萃分析  

Association between CYP2E1 and NAT2 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs:a meta-analysis

作　　者：盛云建 何鸿雁 

机构地区：[1]西南医科大学附属医院感染科,泸州646000 [2]西南医科大学公共卫生学院实验中心

出　　处：《传染病信息》2017年第4期212-215,共4页Infectious Disease Information

基　　金：四川省重点学科建设项目资助(SZD0421)

摘　　要：目的明确细胞色素氧化酶P450 2E1(cytochrome P450 2E1,CYP2E1)和N-乙酰基转移酶-2(N-acetyltransferase-2,NAT2)基因多态性与抗结核药诱导的药物性肝损伤(anti-tuberculosis drug-induced hepatotoxicity,ATDH)之间的关系。方法计算机检索Medline/Pubmed、EMBASE、Web of Science数据库和Cochrane图书馆中所有有关CYP2E1基因多态性与ATDH关系的研究文献。根据文献纳入及排除标准筛选文献,并对文献进行质量评价。采用OR及95%CI作为分析疗效的统计量。采用Revman 5.0软件统计分析。结果共计纳入研究文献9篇,入选2049例研究对象。CYP2E1基因Pst I/Rsa I多态性中,c1/c1型比c1/c2和c2/c2型有更高的ATDH发生率(OR=1.38,95%CI:1.08~1.77,P=0.01);在Dra I多态性中各型之间无差异(OR=0.78,95%CI:0.51~1.18,P=0.23)。与携带NAT2快速或中速乙酰化的c1/c1型人群比较,携带NAT2慢速乙酰化的c1/c1型人群具有更高的ATDH风险(OR=3.10,P<0.0001)。结论 CYP2E1基因c1/c1型是ATDH发生的风险因素,且合并慢速乙酰化的NAT2基因型时可进一步增加ATDH发生率。Objective To explore the potential association between cytochrome P450 2E1 （CYP2E1） and N-acetyltransferase-2 （NAT2） polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity. Methods Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library for the literatures about CYP2E1 polymorphism and anti-tuberculosis drug-induced hepatotoxicity were retrieved. All literatures were screened according to the inclusive and exclusive criteria, and the quality was measured. The efficacy was analyzed by odds ratios （OR） and 95% confidence interval （CI） using Revman 5.0 software. Results A total of 9 literatures involving 2049 cases were included. Compared with the c1/c2 and c2/c2 genotypes, the c1/c1 genotype induced a higher risk of anti-tuberculosis drug-induced hepatotoxicity （OR=1.38, 95% CI： 1.08-1.77, P=0.01） for the PstI/RsaI polymorphism, and there was no significant difference for the DraI polymorphism （OR=0.78, 95% CI： 0.51-1.18, P=0.23）. Compared with individuals with NAT2 fast or intermediate acetylator genotype and c1/c1 genotype, patients who were NAT2 slow acetylators and carried the high activity CYP2E1 c1/c1 genotype had higher risk for anti-tuberculosis drug-induced hepatotoxicity （OR=3.10, P 〈 0.0001）. Conclusions CYP2E1 c1/c1 genotype is a risk factor for anti-tuberculosis drug-induced hepatotoxicity, and the concomitant presence of slow acetylator NAT2 genotype may further increase this risk.

关 键 词：细胞色素氧化酶P450 2E1 基因多态性 结核 药物性肝损伤 荟萃分析 

分 类 号：R52[医药卫生—内科学]