Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China/Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China/ Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Pak J Pharm Sci. 2021 Sep;34(5):1759-1766.
Valproate (VPA)-induced hepatotoxicity is a fatal adverse drug reaction，and children is a high-risk population. Our study aimed to explore whether key genetic polymorphisms of antioxidant pathway is associated with VPA-mediated AST elevation. We included 194 newly diagnosed epilepsy children (aged from 1 to 16 years old) and treated with VPA. These patients were divided into two groups: one group for AST is normal and another group is AST elevated. AST elevation occurred in 25.8% of patient treated with VPA. During VPA monotherapy, the maximum AST in patients of GSTP1 rs1695 with AA genotype was significantly higher than carrying G alleles (36.50 ±14.89 vs 32.88±10.69, P=0.003). Patients with AG+GG genotype of GSTP1 rs1695 had a reduced risk of elevated AST (adjusted OR=0.37, 95% CI: 0.16-0.84, P=0.017). There is a significant difference in the maximum AST value of CAT rs769217 genotype (P=0.011, P= 0.045, respectively). Children with CAT rs769217 CT genotype or CT+TT genotype have a lower risk of elevated AST (adjusted OR=0.30, 95% CI: 0.13-0.68, P=0.004 and adjusted OR=0.41, 95% CI:0.20-0.82,P=0.012, respectively). Children who with GSTP1 rs1695 G allele have a reduced risk of AST abnormalities. We conducted CAT rs769217 CC genotype is a risk factor for AST elevation in children.
丙戊酸（VPA）诱导的肝毒性是一种致命的药物不良反应，儿童是高危人群。我们的研究旨在探讨抗氧化途径的关键遗传多态性是否与 VPA 介导的 AST 升高有关。我们纳入了 194 名新诊断的癫痫儿童（年龄 1 至 16 岁），并接受 VPA 治疗。这些患者分为两组：一组 AST 正常，另一组 AST 升高。接受 VPA 单药治疗的患者中，AST 升高的发生率为 25.8%。在 VPA 单药治疗期间，GSTP1 rs1695 中 AA 基因型的患者的最大 AST 明显高于携带 G 等位基因的患者（36.50±14.89 vs 32.88±10.69，P=0.003）。GSTP1 rs1695 的 AG+GG 基因型的患者发生 AST 升高的风险降低（调整后的 OR=0.37，95%CI：0.16-0.84，P=0.017）。CAT rs769217 基因型的最大 AST 值存在显著差异（P=0.011，P=0.045）。CAT rs769217 CT 基因型或 CT+TT 基因型的儿童发生 AST 升高的风险较低（调整后的 OR=0.30，95%CI：0.13-0.68，P=0.004 和调整后的 OR=0.41，95%CI：0.20-0.82，P=0.012）。携带 GSTP1 rs1695 G 等位基因的儿童发生 AST 异常的风险降低。我们发现 CAT rs769217 CC 基因型是儿童 AST 升高的危险因素。
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