SCN1A rs6732655A/T polymorphism: Diagnostic and therapeutic insights for drug-resistant epilepsy.

Background: A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.

Aim: To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.

Methods: The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1β, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.

Results: AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1β and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1β and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.

Conclusion: SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.