GABRG2, rs211037 is associated with epilepsy susceptibility, but not with antiepileptic drug resistance and febrile seizures

Shabeesh Balan, Sanish Sathyan, Saradalekshmi K. Radha, Vijai Joseph, Kurupath Radhakrishnan, Moinak Banerjee

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


OBJECTIVE: Several antiepileptic drugs (AEDs) are known to target the GABAA receptor through positive allosteric modulation of the receptors, thereby enhancing GABAA receptor-mediated inhibition. The large diversity of GABAA receptors has been reported in the central nervous system; some of these have been implicated in epilepsy susceptibility and AED resistance, which we aimed to examine. MATERIALS AND METHODS: We investigated the association of single-nucleotide polymorphisms in GABA A receptor subunit subtype genes namely; rs2279020 (GABRA1), rs3219151 (GABRA6), rs2229944 (GABRB2), and rs211037 (GABRG2) with predisposition to epilepsy and AED resistance. This was assessed in three cohorts of ethnically matched South Indian ancestry: mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype of AED-resistant epilepsy syndrome), juvenile myoclonic epilepsy (prototype of AED-responsive epilepsy syndrome), and nonepilepsy controls. RESULTS: A significant allelic (P=0.0006, odds ratio=1.6, 95% confidence interval=1.22-2.08) and genotypic (P=0.001) association of a synonymous variant in GABRG2, rs211037 (Asn196Asn) was observed with epilepsy irrespective of its phenotype, that is, MTLE-HS or juvenile myoclonic epilepsy. However, this association was not retained in epilepsy patients with a history of febrile seizures. The GABAA receptor subunit subtype genes were not found to have any association with AED resistance. In-silico analysis indicated that rs211037 plays a significant role in the transcriptional regulation and splicing regulation. CONCLUSION: We could substantiate that among the GABAA receptor subunit gene cluster polymorphisms, the GABRG2, rs211037 predisposes susceptibility to epilepsy, irrespective of its phenotype, but not to AED resistance.

Original languageEnglish (US)
Pages (from-to)605-610
Number of pages6
JournalPharmacogenetics and Genomics
Issue number11
StatePublished - Nov 2013
Externally publishedYes


  • Antiepileptic drug resistance
  • Epilepsy
  • GABRG2
  • Hippocampal sclerosis
  • Juvenile myoclonic epilepsy
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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