Susceptibility of N-acetyltransferase 2 slow acetylators to antituberculosis drug-induced liver injury: a meta-analysis

Pharmacogenomics. 2015 Dec;16(18):2083-97. doi: 10.2217/pgs.15.144. Epub 2015 Nov 30.

Abstract

Aim: This study aimed to evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATLI).

Materials & methods: A meta-analysis was performed including 27 studies with 1289 cases and 5462 controls. Odds ratio with 95% CI was used to evaluate the strength of association.

Results: Our meta-analysis found that NAT2 slow acetylators were associated with increased risk of ATLI compared with fast and intermediate acetylators when standard dose of isoniazid was administrated (odds ratio: 3.08; 95% CI: 2.29-4.15).

Conclusion: Individuals with NAT2 slow acetylators may have increased risk of ATLI when standard dose of isoniazid was used. Detection of NAT2 genotype may benefit to the prevention of ATLI.

Keywords: N-acetyltransferase 2; antituberculosis drug-induced liver injury; isoniazid; meta-analysis; polymorphism.

Publication types

  • Meta-Analysis

MeSH terms

  • Acetylation
  • Antitubercular Agents / adverse effects*
  • Arylamine N-Acetyltransferase / genetics*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / etiology
  • Humans
  • Isoniazid / adverse effects*
  • Polymorphism, Genetic
  • Risk
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / enzymology

Substances

  • Antitubercular Agents
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • Isoniazid