Association of N-acetyltransferase-2 genotypes and anti-tuberculosis induced liver injury; first case-controlled study from Iran

Curr Drug Saf. 2011 Feb 1;6(1):17-22. doi: 10.2174/157488611794479946.

Abstract

Purpose: The goals of this study were to identify the frequency of N-acetyltransferase-2 genotypes and phenotypes in Iranian tuberculosis and healthy subjects and to evaluate correlation of acetylator phenotype and antituberculosis-induced hepatotoxicity in pulmonary tuberculosis patients.

Method: A total of 50 newly diagnosed pulmonary tuberculosis patients and 50 healthy Iranian subjects were enrolled in the study. A combination of polymerase chain reaction and restriction fragment length polymorphism were used to investigate N-acetyltransferase-2 alleles. The tuberculosis patients were followed for occurrence of antituberculosis induced hepatotoxicity during the treatment course. Correlation between N-acetyltransferase-2 phenotypes and antituberculosis induced hepatotoxicity was evaluated.

Results: Frequency of slow, intermediate and fast acetylator genotypes in the healthy group were 32%, 54% and 14% and in the tuberculosis patients were 28%, 64% and 8%, respectively. Hepatotoxicity was detected in 64.3% of slow acetylators, 15.6% of intermediate acetylators and interestingly in none of the fast acetylators.

Conclusion: There were no significant difference in distribution of various N-acetyltransferase-2 alleles, genotypes and phenotypes between pulmonary TB patients and healthy individuals. Among patients, anti-tuberculosis induced hepatotoxicity was more frequent in slow acetylators in comparison with fast acetylators in Iranian tuberculosis patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / adverse effects*
  • Arylamine N-Acetyltransferase / genetics*
  • Arylamine N-Acetyltransferase / metabolism
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Female
  • Genotype
  • Humans
  • Iran / epidemiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Tuberculosis, Pulmonary / enzymology*
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / genetics*
  • Young Adult

Substances

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