The genetic methods for drug-resistant epilepsy

Abstract

ActualityMechanisms of underlying pharmacoresistance have been explored insufficiently. Enzymes of a system for biotransformation of xenobiotic and transporters for drugs are the key participants in the systems of metabolism of antiepileptic drugs (AEDs). Among proteins-transporters, glycoprotein P encoded by MDR1 gene plays an essential role in the processes of uptake, distribution and excretion of AEDs.ObjectiveThe work initiated to study gene MDR1 C3435 T polymorphism and to assess its association with pharmacoresistance formation in patients with epilepsy receiving antiepileptic drugs (AEDs).MaterialsStudy involved 89 patients with localization-related epilepsy and 55 unrelated healthy subjects.ResultsDistribution of 3435 T/C polymorphism in NDR1 gene was analyzed in the patients with the localization-related epilepsy and nominally healthy donors. The distribution of frequencies of gene alleles was found to correspond to the Hardy-Weinberg equilibrium (Р > 0.05). Incidence of genotypic variants of the polymorphism was as follows, СС was found in 18.6%, СТ and TT were observed in 55.9% and 25.4% of cases. In the controls СС was found in 60.0%, СТ and TT were observed in 33.3% and 6.6% of cases, respectively. The findings are the evidence for significant effect of functionally weak variants in C3435 T polymorphism of MDR1 gene on efficacy of antiepileptic therapy.Conclusionpresence of T-allele of C3435 T polymorphism of MDR1 gene increases risk of pharmacoresistance in the patients with epilepsy and is a significant and predicting criterion of efficacy and feasibility of the antiepileptic therapy conducted.Disclosure of interestThe authors have not supplied their declaration of competing interest.