PURPOSE: This study aims to evaluate the associations between genetic polymorphisms and the effect of sodium valproate (VPA) therapy in children with generalized seizures.
METHODS: A total of 174 children with generalized seizures on VPA therapy were enrolled. Steady-state trough plasma concentrations of VPA were analyzed. Seventy-six single nucleotide polymorphisms involved in the absorption, metabolism, transport, and target receptor of VPA were identified, and their associations with the therapeutic effect (seizure reduction) were evaluated using logistic regression adjusted by various influence factors.
RESULTS: rs7668282 (UGT2B7, T?>?C, OR?=?2.67, 95% CI: 1.19 to 5.91, P?=?0.017) was more prevalent in drug-resistant patients than drug-responsive patients. rs2242480 (CYP3A4, C?>?T, OR?=?0.27, 95% CI: 0.095 to 0.79, P?=?0.017) and rs10188577 (SCN1A, T?>?C, OR?=?0.40, 95% CI: 0.17 to 0.94, P?=?0.035) were more prevalent in drug-responsive patients compared to drug-resistant patients.
CONCLUSION: In children with generalized seizures on VPA therapy, polymorphisms of UGT2B7, CYP3A4, and SCN1A genes were associated with seizure reduction. Larger studies are warranted to corroborate the results.