Association of SCN1A Polymorphisms rs3812718 and rs2298771 with Epilepsy

<b>Background/Objectives:</b> Epilepsy is a brain disease with both environmental and genetic inputs. Ion channel dysfunction seems to be of great significance for abnormal neuronal behavior during epileptic seizures. Within neurons, the voltage-gated sodium channels are crucial proteins contributing to the initiation and propagation of action potentials. The voltage-gated sodium channel α subunit 1 (<i>SCN1A</i>) gene encodes for the α subunit of a voltage-gated ion channel. The aim of the study was to investigate the relation of two common <i>SCN1A</i> variants, i.e., rs3812718 and rs2298771, with distinct epileptic phenotypes in a South-Eastern European population. <b>Methods:</b> DNA was extracted from 214 unrelated participants with focal onset, focal to bilateral tonic-clonic, or generalized onset epileptic seizures and genotyped using real-time PCR (LightSNiP assays) followed by melting curve analysis. Statistical analysis of the results was performed using IBM SPSS Statistics software (version 29.0 for Windows). <b>Results:</b> Genotype frequency distribution analysis indicated an association for the A-allele-containing genotypes of both rs3812718 and rs2298771 polymorphisms of <i>SCN1A</i> with generalized onset seizures and focal to bilateral tonic-clonic seizures versus focal onset seizures. <b>Conclusions:</b> Consequently, the study provides evidence that supports a potential association of the investigated <i>SCN1A</i> polymorphisms with distinct seizure subtype susceptibility in South-Eastern Europeans.