The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: a meta-analysis

Infect Genet Evol. 2014 Jun:24:34-40. doi: 10.1016/j.meegid.2014.01.034. Epub 2014 Mar 6.

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).

Conclusion: 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.

Keywords: ATDH; CYP2E1; Hepatotoxicity; Meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / adverse effects*
  • Antitubercular Agents / therapeutic use
  • Arylamine N-Acetyltransferase / genetics*
  • Cytochrome P-450 CYP2E1 / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Hepatocytes / drug effects
  • Humans
  • Isoniazid / adverse effects
  • Isoniazid / therapeutic use
  • Liver Failure, Acute / chemically induced*
  • Odds Ratio
  • Polymorphism, Genetic
  • Pyrazinamide / adverse effects
  • Pyrazinamide / therapeutic use
  • Rifampin / adverse effects
  • Rifampin / therapeutic use
  • Tuberculosis / drug therapy*

Substances

  • Antitubercular Agents
  • Pyrazinamide
  • Cytochrome P-450 CYP2E1
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • Isoniazid
  • Rifampin