title: Update meta-analysis of the CYP2E1 RsaI/PstI and DraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  This meta-analysis suggests that there is an increased risk of ATDH in individuals carrying the C1/C1 genotype of the CYP2E1 RsaI/PstI polymorphism. However, no association was found for the DraI polymorphism.
authors.affiliation: Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: F-J
authors.initials: FJ
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: T
authors.initials: T
authors.lastname: Niu
authors.affiliation: West China School of Public Health, Sichuan University, Chengdu, Sichuan, China.
authors.forename: W-X
authors.initials: WX
authors.lastname: Lu
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Sandford
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: J-Q
authors.initials: JQ
authors.lastname: He
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D000995:Antitubercular Agents; D019392:Cytochrome P-450 CYP2E1
keywords: CYP2E1; antituberculosis drug-induced hepatotoxicity; meta-analysis; polymorphism