Influence of glutathione S-transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population
Article first published online: 7 APR 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Volume 28, Issue 6, pages 835–839, July 2008
How to Cite
Leiro, V., Fernández-Villar, A., Valverde, D., Constenla, L., Vázquez, R., Piñeiro, L. and González-Quintela, A. (2008), Influence of glutathione S-transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population. Liver International, 28: 835–839. doi: 10.1111/j.1478-3231.2008.01700.x
- Issue published online: 4 JUN 2008
- Article first published online: 7 APR 2008
- Received 28 October 2007Accepted 5 January 2008
- drug-related liver injury;
- genetic polymorphisms;
- genetic risk factors;
- racial differences;
Objectives: Genetic variations in enzymes of isoniazid metabolism confer an increased risk for antituberculosis drug-induced hepatotoxicity in Asian populations. The present study was aimed at investigating the possible association of antituberculosis drug-induced hepatotoxicity with polymorphisms at the glutathione S-transferase (GST) gene in a Caucasian population.
Methods: A prospective case–control study was nested in a cohort of patients with active tuberculosis who were treated with a combination of isoniazid, rifampicin and pyrazinamide. Cases constituted patients with antituberculosis drug-induced hepatotoxicity (n=35), and controls constituted patients without any evidence of this complication (n=60). Homozygous null polymorphisms at GST loci M1 and T1 were analysed from genomic DNA from all participants.
Results: The GSTT1 homozygous null polymorphism was significantly associated with antituberculosis drug-induced hepatotoxicity [odds ratio (OR) 2.60, 95% confidence interval (CI) 1.08–6.24, P=0.03]. No significant association was observed between the GSTM1 homozygous null polymorphism and antituberculosis drug-induced hepatotoxicity (OR 0.73, 95% CI 0.31–1.73, P=0.48).
Conclusion: The GSTT1 homozygous null polymorphism may be a risk factor of antituberculosis drug-induced hepatotoxicity in Caucasians.