Association of SCN1A and SCN2A Gene Polymorphisms with Antiseizure Medication Responsiveness: A Case-Control Study from Eastern India

BACKGROUND AND OBJECTIVES: Epilepsy, with its complex interplay of neurobiological, genetic, and pharmacological factors, continues to challenge neurologists worldwide-particularly in managing drug resistance. This study aimed to evaluate the frequency of the SCN1A and SCN2A gene polymorphisms among patients with epilepsy (PWE) from Eastern India to assess their relationship with clinical profiles, electroencephalography (EEG) findings, and response to antiseizure medication. METHODS: In this case-control genetic association study, a total of 110 PWE were assessed for demographic and clinical profiles, EEG and neuroimaging findings, and treatment response. SCN1A and SCN2A gene polymorphisms (five selected intronic single nucleotide polymorphisms [SNPs]-four in SCN1A [rs2298771, rs6730344, rs10167228, rs6732655] and one in SCN2A [rs17183814]) were assessed through polymerase chain reaction and restriction fragment length polymorphism. RESULTS: In the present study cohort, we observed that the generalized seizure type (73.6%) and early-onset seizures (mean 7.4 years in drug-resistant epilepsy [DRE]) were significantly more frequent in drug-resistant persons. The SCN2A rs17183814 AG genotype frequencies were 36/92 (39.1%) in DRE, 10/18 (55.6%) in responders, and 46/110 (41.8%) in controls. Statistical comparison showed no significant association between the AG genotype and drug resistance (DRE vs. responders: odds ratio [OR] 0.51, 95% confidence interval [CI] 0.19-1.43, P = 0.303; DRE vs. controls: OR 0.89, 95% CI 0.51-1.57, P = 0.808). CONCLUSIONS: On genetic analysis, the AG genotype of SCN2A rs17183814 was numerically higher among responders than DRE, but the difference was not significant. None of the SCN1A SNPs studied ( rs2298771, rs6730344, rs10167228, rs6732655 ) showed significant associations with treatment response, consistent with previous Indian reports.