Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The SCN1A and SCN2A genes encode α subunits of the neuronal voltage-gated sodium channel, which are targets for various antiepileptic drugs such as carbamazepine, phenytoin, valproate and others. • Recent studies have demonstrated that various genetic variants of these channel genes play important role in the pathogenesis and therapy of epilepsy. WHAT THIS STUDY ADDS • This study demonstrates a significant association between the SCN1A c.3184 A→G; AG genotype and epilepsy. • However SCN2A c.56 G→A; allele 'A' was significantly associated with multiple drug resistance in epilepsy in north Indian population. AIMS To evaluate sodium channel genes as candidates for epilepsy susceptibility and their role in therapeutic efficacy, we screened coding single-nucleotide polymorphism of SCN1A p. Thr 1067 Ala or c.3184 A→G (rs2298771) and SCN2A p.Arg19Lys or c.56 G→A (rs17183814) in north Indian epilepsy patients. METHODS The genotyping was performed in 160 control subjects and 336 patients with epilepsy, of whom 117 were drug resistant and 219 were drug responsive. Therapeutic drug monitoring for phenytoin, carbamazepine, phenobarbital and valproate was also performed in 20% of the patients to confirm compliance. RESULTS AG genotype of SCN1A 3184 A→G polymorphism was significantly higher and associated in epilepsy patients [P = 0.005; odds ratio (OR) 1.76, 95% confidence interval (CI) 1.19, 2.61], whereas A variant of SCN2A c.56 G→A was associated with multiple drug resistance in north Indian patients with epilepsy (P = 0.03; OR 1.62, 95% CI 1.03, 2.56). CONCLUSIONS Overall, results indicate a differential role of genetic polymorphisms of sodium channels SCN1A and SCN2A in epilepsy susceptibility and drug response. © 2009 The British Pharmacological Society.