IntroductionThis case-control study aimed to assess two single nucleotide polymorphisms of the gene encoding the GABRG2 protein – GABRG2 (3145 G>A) and GABRG2 rs 211037 Asn196Asn (C588T) – in a cohort of pediatric patients from Romania, and evaluate their possible impact on drug-resistant forms of generalized epilepsy and recurrent febrile seizures.Material and methodsOne hundred and fourteen children with idiopathic generalized epilepsy (group 1) or febrile seizures (group 2) were compared to 153 controls. Peripheral blood samples were assessed using polymerase chain reaction-restriction fragment length polymorphism analysis, with results interpreted based on the disappearance of a restriction site in the C allele (122 bp) compared to the T allele (100 bp + 22 bp).ResultsA significant association was found with the TT homozygous genotype and T allele for both febrile seizures and epilepsy for the C588T locus, while GABRG2 G>A 3145 showed no significant association with any type of seizure. The TT homozygous genotype of GABRG2 Asn196Asn polymorphism was more frequent in patients with a history of febrile seizures (p = 0.0001), without a significant association identified for GABRG2-G>A 3145. Composite analysis showed associations with epilepsy for CC-AG (p = 0.02) and CT-AG (p = 0.007) with the CC-AA combination as reference.ConclusionsC588T polymorphism of the GABRG2 gene might be a predictive genetic marker in triggering febrile convulsions. GABRG2 rs211037 TT homozygotes and T allele variants have an increased risk for developing febrile seizures. Recurrent crises and repeated episodes of seizures are more frequent in the GABRG2 Asn196Asn TT genotype polymorphism, with a 45 and 8 times higher risk of developing idiopathic generalized epilepsy and recurrent febrile seizures, respectively.

Background: P-glycoprotein (P-gp)