Potential role of GABA A receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population

Abstract

Background GABA A receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also. Methods We investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABA A receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods. Results The GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P = 0.018), CC (P = 0.0001) genotype and for C allele (P = 0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P = 0.012), TT (P = 0.778) genotype and for variant T allele (P = 0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism. Conclusion Overall, our findings suggest significant involvement of alpha ( GABRA6) and beta ( GABRB2) subunits of GABA A receptor in epilepsy susceptibility in north Indian population.