Effects of glutathione S-transferase M1 and T1 deletions on carbamazepine metabolism among a Tunisian population

Abstract

Glutathione-S-transferases enzymes are involved in the detoxification of several endogenous and exogenous substances. These genetic pathways could be involved in the therapeutic efficacy and toxic effects of carbamazepine by modulating metabolic profiles. In this present study, we evaluated the effects of two glutathione-S-transferase polymorphisms, GSTM1 and GSTT1, on metabolic phenotype of carbamazepine in a Tunisian population. These polymorphisms were studied in 94 patients with epilepsy, using a polymerase chain reaction. Test U Mann–Whitney was used for analyzing results. The study results demonstrated that individuals with the glutathione-S-transferase M1 null genotype were at an increased risk of toxicity secondary to a relative accumulation of carbamazepine 10,11-epoxide and carbamazepine. Consequently leading to an increase in the plasma concentration of carbamazepine and carbamazepine 10,11-epoxide (P = 0.03, P = 0.01 respectively). Whereas no significant effects were observed between individuals with glutathione-S-transferase M1 or glutathione-S-transferase T1 null genotype and metabolic ratio carbamazepine 10,11-epoxide to carbamazepine (P = 0.40). These genotyping findings revealed that the absence of GSTM1 activity could be a contributor factor for the development of toxic effects of carbamazepine. Such an accumulation would require eventually a dosage adjustment.

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