title: Association of alpha subunit of GABAA receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population.
abstract: GABA (gamma-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.
authors.affiliation: Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Kumari
authors.forename: Ram
authors.initials: R
authors.lastname: Lakhan
authors.forename: J
authors.initials: J
authors.lastname: Kalita
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics*
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A