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Influence of glutathione S ‐transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug‐induced hepatotoxicity in a Caucasian population
Author(s) -
Leiro Virginia,
FernándezVillar Alberto,
Valverde Diana,
Constenla Lucía,
Vázquez Rafael,
Piñeiro Luis,
GonzálezQuintela Arturo
Publication year - 2008
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2008.01700.x
Subject(s) - pyrazinamide , odds ratio , medicine , isoniazid , gastroenterology , pharmacology , glutathione s transferase , rifampicin , case control study , population , drug , genotype , drug metabolism , tuberculosis , glutathione , biology , genetics , pathology , gene , enzyme , biochemistry , environmental health
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.