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

Br J Clin Pharmacol. 2009 Aug;68(2):214-20. doi: 10.1111/j.1365-2125.2009.03437.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Multiple / genetics*
  • Epilepsy / drug therapy
  • Epilepsy / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Phenotype
  • Polymorphism, Genetic
  • Reference Values
  • Sodium Channels / drug effects
  • Sodium Channels / genetics*
  • Young Adult

Substances

  • Sodium Channels