Influence of glutathione S‐transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug‐induced hepatotoxicity in a Caucasian population
- 4 June 2008
- journal article
- Published by Wiley in Liver International
- Vol. 28 (6), 835-839
- https://doi.org/10.1111/j.1478-3231.2008.01700.x
Abstract
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. 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. 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). The GSTT1 homozygous null polymorphism may be a risk factor of antituberculosis drug-induced hepatotoxicity in Caucasians.This publication has 10 references indexed in Scilit:
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