Department of Neurology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China; Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100045, China.
Seizure. 2018 May;58:96-100. doi: 10.1016/j.seizure.2018.04.006. Epub 2018 Apr 14.
This study aims to evaluate the associations between genetic polymorphisms and the effect of sodium valproate (VPA) therapy in children with generalized seizures.
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.
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.
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.
本研究旨在评估遗传多态性与丙戊酸钠（VPA）治疗儿童全面性发作的疗效之间的关联。
共纳入 174 例接受 VPA 治疗的全面性发作患儿。分析 VPA 的稳态谷血浆浓度。鉴定了 76 个与 VPA 的吸收、代谢、转运和靶受体相关的单核苷酸多态性，并使用逻辑回归评估其与治疗效果（发作减少）的相关性，调整了各种影响因素。
rs7668282（UGT2B7，T>C，OR=2.67，95%CI：1.19 至 5.91，P=0.017）在耐药患者中比在敏感患者中更为常见。rs2242480（CYP3A4，C>T，OR=0.27，95%CI：0.095 至 0.79，P=0.017）和 rs10188577（SCN1A，T>C，OR=0.40，95%CI：0.17 至 0.94，P=0.035）在敏感患者中比在耐药患者中更为常见。
在接受 VPA 治疗的全面性发作患儿中，UGT2B7、CYP3A4 和 SCN1A 基因的多态性与发作减少相关。需要更大的研究来证实这些结果。
