Update meta-analysis of the CYP2E1 Rsa I /Pst I and Dra I polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies

作者：F.-J. Wang, Yan Wang, Ting Niu, Wusheng Lu, Andrew J. Sandford, Jian‐Qing He · 发表于：Journal of Clinical Pharmacy and Therapeutics · 年份：2016 · DOI：10.1111/jcpt.12388 · 被引用次数：21 · 研究领域：Drug-Induced Hepatotoxicity and Protection、Pharmacogenetics and Drug Metabolism、Poisoning and overdose treatments

WHAT IS KNOWN AND OBJECTIVE: Several studies have investigated the association of the CYP2E1 RsaI/PstI and/or DraI polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity (ATDH), but the results have been inconsistent. Therefore, we performed a large meta-analysis to determine a more precise estimation of this relationship. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure and Chinese Biomedical Literature databases were systematically searched to identify relevant studies. Meta-analyses based on the entire population and subgroups were performed to examine the association between CYP2E1 polymorphisms and susceptibility to ATDH. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations. RESULTS AND DISCUSSION: Twenty-six studies with a total of 7423 participants were analysed. The overall ORs of relevant studies demonstrated that the CYP2E1 RsaI/PstI C1/C1 genotype was associated with an elevated risk of ATDH (OR = 1·32, 95% CI 1·03-1·69, P = 0·027), but for the DraI polymorphism there was no increase in risk (OR = 1·05, 95% CI 0·80-1·37, P = 0·748). In subgroup analyses of the RsaI/PstI polymorphism, significant results were found in East Asians, patients who used isoniazid + rifampicin + pyrazinamide + ethambutol and patients with twice the upper limit of normal as the minimum standard for defining ATDH. WHAT IS NEW AND CONCLUSION: This meta-analysis suggests that there is an increa...