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

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,P0.0001)。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。

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

Objective To explore the potential association between cytochrome P4502E1 (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 thec1/c2 andc2/c2 genotypes, thec1/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 andc1/c1 genotype, patients who were NAT2 slow acetylators and carried the high activity CYP2E1c1/c1 genotype had higher risk for anti-tuberculosis drug-induced hepatotoxicity (OR=3.10,P<0.0001).Conclusions CYP2E1c1/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.