Influence of glutathione S-transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population
| Autor: | Virginia Leiro, Lucía Constenla, Alberto Fernández-Villar, R. Vázquez, Luis Piñeiro, Diana Valverde, Arturo Gonzalez-Quintela |
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| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | Liver International. 28:835-839 |
| ISSN: | 1478-3231 1478-3223 |
| DOI: | 10.1111/j.1478-3231.2008.01700.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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