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Update meta‐analysis of the CYP 2E1 Rsa I /Pst I and Dra I polymorphisms and risk of antituberculosis drug‐induced hepatotoxicity: evidence from 26 studies
Author(s) -
Wang F.J.,
Wang Y.,
Niu T.,
Lu W.X.,
Sandford A. J.,
He J.Q.
Publication year - 2016
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12388
Subject(s) - odds ratio , psti , medicine , meta analysis , genotype , confidence interval , genetics , biology , restriction enzyme , dna , gene
Summary What is known and objective Several studies have investigated the association of the CYP 2E1 Rsa I /Pst I and/or Dra I 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 CYP 2E1 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 OR s of relevant studies demonstrated that the CYP 2E1 Rsa I /Pst I 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 Dra I polymorphism there was no increase in risk ( OR = 1·05, 95% CI 0·80–1·37, P = 0·748). In subgroup analyses of the Rsa I/ Pst I 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 increased risk of ATDH in individuals carrying the C1/C1 genotype of the CYP 2E1 Rsa I /Pst I polymorphism. However, no association was found for the Dra I polymorphism.