Association of alpha subunit of GABA_A receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population

Abstract 

GABA (γ-amino butyric acid) receptors have always been an inviting target in the etiology and treatment of epilepsy because of its role as a major inhibitory neurotransmitter in the brain. The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11+15 A>G (rs2279020) and GABRG2 588C>T (rs211037) genes in seizure susceptibility and pharmaco-resistance in northern Indian patients with epilepsy. A total of 395 epilepsy patients and 199 control subjects were enrolled for present study. The genotyping was done by PCR-RFLP methods. The GABRA1 IVS11+15 A>G polymorphism conferred high risk for epilepsy susceptibility at genotype ‘AG’ (P=0.004, OR=1.77, 95% CI=1.20–2.63), ‘GG’ (P=0.01, OR=1.80, 95% CI=1.15–2.80) and G allele level (P=0.001, OR=1.50, 95% CI=1.16–1.92). Moreover this polymorphism was also associated with multiple drug resistance in patients with epilepsy for homozygous variant ‘GG’ genotype (P=0.031, OR=1.84, 95% CI=1.05–3.23) and G allele (P=0.020, OR=1.43, 95% CI=1.05–1.95). However GABRG2 588C>T polymorphism was not found to be associated either with epilepsy susceptibility or with drug resistance. Overall results indicate differential role of different subunits of GABA_A receptor subtypes in epilepsy susceptibility and pharmacotherapy.

Keywords: GABA_A receptor, Drug resistance, Epilepsy, Antiepileptic drugs, GABRA1 and GABRG2