Association of SCN1A gene polymorphism with antiepileptic drug responsiveness in the population of Thrace, Greece

Arch Med Sci. 2017 Feb 1;13(1):138-147. doi: 10.5114/aoms.2016.59737. Epub 2016 May 5.

Abstract

Introduction: The aim was to examine the influence of the SCN1A gene polymorphism IVS5-91 rs3812718 G>A on the response to antiepileptic drugs (AEDs) in monotherapy or polytherapy.

Material and methods: Two hundred epilepsy patients and 200 healthy subjects were genotyped for SCN1A IVS5-91 rs3812718 G>A polymorphism using TaqMan assay. Patients were divided into drug-responsive and drug-resistant patients. The drug-responsive group was further studied, comparing monotherapy in maximum and minimum doses and monotherapy-responsive and -resistant groups.

Results: There were no statistically significant differences in the allelic frequencies and genotype distributions between patients and controls (p = 0.178). The distribution of SCN1A IVS5-91 rs3812718 G>A genotypes was similar between drug-responsive and drug-resistant patients (p = 0.463). The differences in genotype distributions (A/A or A/G vs. G/G) between monotherapy-responsive and -resistant groups were statistically significant (p = 0.021). Within the monotherapy-responsive group, patients with the A/A or A/G genotype needed higher dose AEDs than patients with the G/G genotype (p = 0.032). The relative risk for generalized epilepsy due to A-containing genotypes was of marginal statistical significance when compared with the G/G genotype (p = 0.05).

Conclusions: Overall, our findings demonstrate an association of SCN1A IVS5-91 rs3812718 G>A polymorphism with AED responsiveness in monotherapy without evidence of an effect on drug-resistant epilepsy.

Keywords: SCN1A; antiepileptic drugs; gene polymorphism; resistant epilepsy; responsiveness.