Abstract
INTRODUCTION: This 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 METHODS: One 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). RESULTS: A 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. CONCLUSIONS: C588T 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.