title: The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: a meta-analysis.
abstract: BACKGROUND
  Although there have been previous studies on the potential association between cytochrome P450 2E1 (CYP2E1) polymorphisms and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH), the results have generally been controversial.
  
  
  METHODS
  We searched Medline/PubMed, EMBASE, Web of Science, and the Cochrane Library using the following key words: cytochrome P450 2E1, CYP2E1, polymorphism, tuberculosis and TB. The strength of the association between the CYP2E1 PstI/RsaI and DraI polymorphism and ATDH risk as measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied.
  
  
  RESULTS
  Compared with the wild genotype (c1/c1), the OR of ATDH was 1.41 (95% CI: 1.1-1.82, P=0.007) for the PstI/RsaI polymorphism, and 0.78 (95% CI: 0.51-1.18, P=0.23) for the DraI polymorphism. Compared with individuals with N-acetyltransferase 2 (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 ATDH (OR=3.10, P<0.0001).
  
  
  CONCLUSIONS
  The present meta-analysis indicates that the CYP2E1 c1/c1 genotype may be a risk factor for ATDH, and the concomitant presence of the slow acetylator NAT2 genotype may further increase this risk.
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Yun-Jian
authors.initials: YJ
authors.lastname: Sheng
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: School of Public Health of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: He
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Zou
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China.
authors.forename: Yong-Mao
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, The Affiliated Hospital of LuZhou Medical College, LuZhou 646000, China. Electronic address: dengcunl7744@163.com.
authors.forename: Cun-Liang
authors.initials: CL
authors.lastname: Deng
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects / Q000627:therapeutic use; D017114:Liver Failure, Acute / Q000139:chemically induced*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011718:Pyrazinamide / Q000009:adverse effects / Q000627:therapeutic use; D012293:Rifampin / Q000009:adverse effects / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D019392:Cytochrome P-450 CYP2E1; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid; D012293:Rifampin
keywords: ATDH; CYP2E1; Hepatotoxicity; Meta-analysis