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

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.