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

Abstract: Background: GABAA 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 GABAA 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 GABAA receptor in epilepsy susceptibility in north Indian population. [Copyright &y& Elsevier]