ArticleNeuropsychiatric disease and treatment2025
Association of SCN1A Gene Polymorphisms with Sodium Valproate Resistance in Pediatric Epilepsy: A Retrospective Case-Control Study.
Article in Neuropsychiatric disease and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Epilepsy affects approximately 0.4-0.7% of the Chinese population, with an estimated 20-25% of patients developing resistance to antiepileptic drugs. Elucidating the genetic mechanisms underlying sodium valproate resistance could revolutionize personalized treatment strategies, particularly in pediatric epilepsy. Objective: To explore the relationship between polymorphisms in the sodium channel α1 subunit gene (SCN1A) and resistance to sodium valproate therapy in pediatric epilepsy patients. Methods: A retrospective analysis included 89 pediatric patients with sodium valproate-resistant epilepsy (resistant group) and 89 patients responsive to sodium valproate (responder group), and 89 healthy controls. SCN1A gene polymorphisms were analyzed and compared among groups. Plasma valproate concentrations were evaluated across different genotypes. Multivariate logistic regression was performed to identify factors associated with drug resistance. Results: Significant differences in SCN1A genotype distributions were observed among groups for five foci: rs166859148, rs166894396, rs166848482, rs166915162, and rs166870333-335 (P < 0.05). Mutations at these loci were significantly correlated with sodium valproate resistance (P < 0.05). Additionally, patients with mutant genotypes at rs166915162 and rs166870333-335 exhibited lower plasma valproate concentrations compared to those with wild-type alleles (P < 0.05). The rs166870333-335 variant was also significantly associated with generalized seizure types in drug-resistant patients (P < 0.05). Conclusion: Mutation in the SCN1A gene, specifically rs166859148, rs166894396, rs166848482, rs166915162, rs166870333-335, may contribute to resistance to sodium valproate in pediatric epilepsy. Mutations in rs166915162 and rs166870333-335 were associated with reduced plasma levels of sodium valproate, while the rs166870333-335 mutation is linked to generalized seizure types in patients with drug-resistant epilepsy.
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