Weixing Feng1, Shenghui Mei2, Leting Zhu3, Yazhen Yu4, Weili Yang4, Baoqin Gao4, Xiaojuan Wu4, Zhigang Zhao5, Fang Fang6. 1. 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. 2. 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. 3. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. 4. Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. 5. 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. Electronic address: ttyyzzg1022@126.com. 6. Department of Neurology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: 13910150389@163.com.
Abstract
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.
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.
Authors: Alison E Fohner; Rachel Dalton; Kasse Skagen; Konner Jackson; Katrina G Claw; Scarlett E Hopkins; Renee Robinson; Burhan A Khan; Bhagwat Prasad; Erin G Schuetz; Deborah A Nickerson; Timothy A Thornton; Denise A Dillard; Bert B Boyer; Kenneth E Thummel; Erica L Woodahl Journal: Clin Transl Sci Date: 2021-01-27 Impact factor: 4.689