Impact of glutathione S-transferase M1 and T1 on anti-tuberculosis drug-induced hepatotoxicity in Chinese pediatric patients

PLoS One. 2014 Dec 19;9(12):e115410. doi: 10.1371/journal.pone.0115410. eCollection 2014.

Abstract

Background: Anti-tuberculosis drug induced hepatotoxicity (ATDH) is a major adverse drug reaction associated for anti-tuberculosis therapy. The glutathione S-transferases (GST) plays a crucial role in the detoxification of hepatotoxic metabolites of anti-tuberculosis drugs.An association between GSTM1/GSTT1 null mutations and increased risk of ATDH has been demonstrated in adults. Given the ethnic differences and developmental changes, our study aims to investigate the potential impacts of GSTM1/GSTT1 genotypes on the development of ATDH in Han Chinese children treated with anti-tuberculosis therapy.

Methods: Children receiving anti-tuberculosis therapy with or without evidence of ATDH were considered as the cases or controls, respectively. The GSTM1 and GSTT1 genotyping were performed using the polymerase chain reaction.

Results: One hundred sixty-three children (20 cases and 143 controls) with a mean age of 4.7 years (range: 2 months-14.1 years) were included. For the GSTM1, 14 (70.0%) cases and 96 (67.1%) controls had homozygous null mutations. For the GSTT1, 13 (65.0%) cases and 97 (67.8%) controls had homozygous null mutations. Neither the GSTM1, nor the GSTT1 polymorphism was significantly correlated with the occurrence of ATHD.

Conclusion: Our results did not support the GSTM1 and GSTT1 polymorphisms as the predictors of ADTH in Chinese Han children treated with anti-tuberculosis drugs. An age-related association between pharmacogenetics and ATHD need to be confirmed in the further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antitubercular Agents / toxicity*
  • Asian People / ethnology
  • Asian People / genetics*
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury / genetics*
  • Child
  • Child, Preschool
  • China / ethnology
  • Genetic Predisposition to Disease
  • Glutathione Transferase / genetics*
  • Homozygote
  • Humans
  • Infant
  • Mutation

Substances

  • Antitubercular Agents
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81271889), and Beijing Natural Science Foundation (No. 7121007).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.