Zhu Jiahao, Lu Jieluan, He Yaodong, Shen Xianhuan, Xia Hanbing, Li Wenzhou, Zhang Jianping, Fan Xiaomei
Department of Clinical Pharmacology, College of Pharmacy, Jinan University, Guangzhou 511436, China.
Department of Pharmacy, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen 518102, China.
Pharmaceuticals (Basel). 2023 Oct 30;16(11):1536. doi: 10.3390/ph16111536.
Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (, also known as ) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of , rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid ( = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions ( = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions ( = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions ( = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment ( = 0.009). Additionally, no significant association was found between polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.
据报道，ATP结合盒亚家族B成员1（也称为 ）中的基因多态性可能与抗癫痫药物反应的调节有关。本研究旨在探讨中国癫痫儿童中 基因多态性与丙戊酸疗效及药物不良反应之间的关联。共招募了170名来自中国南方、接受丙戊酸治疗超过一年的癫痫儿童，其中61例仍有癫痫发作，109例无癫痫发作。使用Sequenom MassArray系统对 基因的两个单核苷酸多态性rs1128503和rs3789243进行基因分型。发现这两个单核苷酸多态性与癫痫儿童丙戊酸的治疗结果显著相关。rs1128503的TT基因型携带者在丙戊酸治疗后更倾向于出现持续性癫痫发作（ = 0.013）。观察到rs3789243的CC基因型是丙戊酸引起的胃肠道药物不良反应的潜在保护因素（ = 0.018），但可能增加丙戊酸引起的皮肤药物不良反应的风险（ = 0.011）。相比之下，rs3789243的CT基因型与丙戊酸引起的皮肤药物不良反应风险较低有关（ = 0.011）。单倍型分析表明，CC单倍型携带者对丙戊酸治疗的反应往往更好（ = 0.009）。此外，未发现 基因多态性与丙戊酸血清浓度之间存在显著关联。本研究表明， 基因的多态性和单倍型可能与中国癫痫儿童丙戊酸的治疗结果有关。
