The genetic variant "C588T" of GABARG2 is linked to childhood idiopathic generalized epilepsy and resistance to antiepileptic drugs

Seizure. 2018 Aug:60:39-43. doi: 10.1016/j.seizure.2018.06.004. Epub 2018 Jun 6.

Abstract

Purpose: Previous studies have suggested that GABARG2 (Gamma-Aminobutyric acid type A Receptor Gamma 2 subunit) could be a gene of interest in genetic epilepsy; through possible associations with increased epilepsy susceptibility or resistance to antiepileptic drugs. The present study was designed to explore whether the GABARG2 C588 T (rs211037) genetic variant predicts susceptibility to epilepsy and pharmacoresistance among Egyptian children with Idiopathic Generalized Epilepsy (IGE).

Methods: A cohort of 210 Egyptian children was divided into two groups for this case-control study: group (I) included 100 children with IGE, group (II) comprised of 110 paediatric healthy controls. PCR-RFLP was used to amplify the C588 T polymorphism of the GABARG2 gene, which was digested with APOI restriction enzymes.

Results: There was a higher frequency of the TT genotype (P = 0.004) and T allele (P = 0.002) of the C588 T polymorphism of the GABARG2 gene in patients than controls. Besides, there was a substantial increase of the T allele among drug-resistant patients compared with those responding to antiepileptic drugs (P = 0.00015). Children with the C allele were four times more likely to be responsive to antiepileptic drugs than non-C-allele-carriers.

Conclusion: The C588 T polymorphism of GABARG2 is associated with an increased risk of developing childhood IGE and may modulate patients' response to antiepileptic drugs.

Keywords: Children; Epilepsy; GABARG2; Idiopathic; RFLP.

MeSH terms

  • Adolescent
  • Anticonvulsants / therapeutic use
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Drug Resistant Epilepsy / drug therapy
  • Drug Resistant Epilepsy / genetics*
  • Egypt
  • Epilepsy, Generalized / drug therapy
  • Epilepsy, Generalized / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Male
  • Pharmacogenomic Testing
  • Polymorphism, Single Nucleotide*
  • Receptors, GABA-A / genetics*

Substances

  • Anticonvulsants
  • GABRG2 protein, human
  • Receptors, GABA-A

Supplementary concepts

  • Epilepsy, Idiopathic Generalized