Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.
College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.
Eur J Clin Pharmacol. 2020 Aug;76(8):1053-1058. doi: 10.1007/s00228-020-02872-6. Epub 2020 May 8.
Cytochrome P450 (CYP) is involved in the metabolism of valproic acid (VPA). Specifically, CYP2C9 and CYP2A6 are the main enzymes responsible for VPA metabolism. However, the correlation between plasma VPA concentrations and CYP2C9 and CYP2A6 gene variations is uncertain. This meta-analysis aimed to investigate the relationship between CYP2C9 and CYP2A6 variants and plasma concentrations of VPA.
The PubMed, Web of Science, and EMBASE databases were searched for qualifying studies published until July 2019. Cohort studies that included standardized plasma VPA concentrations and CYP2C9 and CYP2A6 genotypes were reviewed. The mean difference and 95% confidence intervals (CIs) were evaluated to assess the strength of the relationship. Data analysis was performed using Review Manager (version 5.3) and RStudio (version 3.6).
In total, we analyzed data from six studies involving 807 patients. We found that CYP2C9*3 was associated with standardized plasma VPA concentration; 3 allele carriers had a 0.70-μg/mL higher concentration per mg/kg than non-carriers (95% CI 0.25, 1.15; P = 0.002). We also found a significant association between the CYP2A64 and standardized trough VPA concentration; patients with the *4 allele had a 0.48-μg/mL higher concentration per mg/kg than patients without the *4 allele (95% CI 0.10, 0.86; P = 0.01).
This meta-analysis demonstrated that CYP2C93 and CYP2A64 genetic variants affect plasma VPA concentrations. For epilepsy patients with these genotypes, dose adjustment may be necessary to ensure VPA's therapeutic effect.
细胞色素 P450（CYP）参与丙戊酸（VPA）的代谢。具体而言，CYP2C9 和 CYP2A6 是负责 VPA 代谢的主要酶。然而，VPA 血浆浓度与 CYP2C9 和 CYP2A6 基因变异之间的相关性尚不确定。本荟萃分析旨在研究 CYP2C9 和 CYP2A6 变异与 VPA 血浆浓度之间的关系。
检索了 PubMed、Web of Science 和 EMBASE 数据库，以获取截至 2019 年 7 月发表的合格研究。综述了包含标准化 VPA 血浆浓度和 CYP2C9 和 CYP2A6 基因型的队列研究。评估了均数差和 95%置信区间（CI），以评估相关性的强度。使用 Review Manager（版本 5.3）和 RStudio（版本 3.6）进行数据分析。
共分析了来自 6 项研究的 807 例患者的数据。我们发现 CYP2C93 与标准化 VPA 血浆浓度相关；每毫克/千克，携带3 等位基因的患者比非携带者高 0.70-μg/mL（95%CI 0.25, 1.15；P = 0.002）。我们还发现 CYP2A64 与标准化 VPA 谷浓度之间存在显著关联；携带4 等位基因的患者比不携带*4 等位基因的患者高 0.48-μg/mL/毫克/千克（95%CI 0.10, 0.86；P = 0.01）。
本荟萃分析表明，CYP2C93 和 CYP2A64 遗传变异影响 VPA 血浆浓度。对于具有这些基因型的癫痫患者，可能需要调整剂量以确保 VPA 的治疗效果。
