Fang Huihui, Wang Xiaojuan, Hou Kelu, Zhang Ying, Shao Shuai, Zhang Guijie, Feng Yufei, Huang Lin
Department of Pharmacy, Peking University People's Hospital, Beijing, China.
Department of Pharmacy, Huainan First People's Hospital, The First Affiliated Hospital of Anhui University of Science and Technology, Huainan, China.
Ann Transl Med. 2021 May;9(10):846. doi: 10.21037/atm-21-1459.
Valproic acid (VPA) is a common antiepileptic drug used to treat both generalized and partial epilepsy. Although there is increasing evidence to suggest that gene polymorphisms are associated with interindividual variability of VPA metabolism, the results are debatable. Therefore, in the present study, we conducted a meta-analysis to evaluate the correlation between gene polymorphisms and adjusted plasma VPA concentration.
The EMBASE, MEDLINE, and Cochrane Library databases were searched to obtain relevant studies. Eligible articles were reviewed, and data extraction was performed. We calculated 95% confidence intervals (CIs) and mean differences (MDs) to assess the strength of the relationship of gene polymorphisms with adjusted plasma VPA concentration.
The meta-analysis included 6 studies involving 847 patients with epilepsy. The pooled analysis showed that the A1075C (AA AC) polymorphism was related to the adjusted plasma concentration of VPA (P=0.02, I= 82%). Additionally, the AC phenotype statistically significantly increased the adjusted plasma VPA concentration in children compared with the mixed age subgroup (P=0.04, I= 48%). A similar association was observed between the AC phenotype for Asians (P<0.00001, I=0%) but not for Caucasians (P=0.34, I=87%).
Age might be a crucial covariate influencing the dosage-adjusted VPA concentration in patients with epilepsy. A reduced VPA dosage may be recommendable for children, particularly Asian children, who are A1075C AC carriers. Further studies could provide high-quality evidence to confirm the correlation between VPA pharmacokinetics and A1075C polymorphisms.
丙戊酸（VPA）是一种常用的抗癫痫药物，用于治疗全身性和部分性癫痫。尽管越来越多的证据表明基因多态性与VPA代谢的个体间差异有关，但结果仍存在争议。因此，在本研究中，我们进行了一项荟萃分析，以评估基因多态性与调整后的血浆VPA浓度之间的相关性。
检索EMBASE、MEDLINE和Cochrane图书馆数据库以获取相关研究。对符合条件的文章进行综述，并进行数据提取。我们计算了95%置信区间（CIs）和平均差异（MDs），以评估基因多态性与调整后的血浆VPA浓度之间关系的强度。
荟萃分析包括6项研究，涉及847例癫痫患者。汇总分析表明，A1075C（AA/AC）多态性与VPA的调整后血浆浓度有关（P = 0.02，I = 82%）。此外，与混合年龄亚组相比，AC表型在统计学上显著增加了儿童调整后的血浆VPA浓度（P = 0.04，I = 48%）。在亚洲人中观察到AC表型之间存在类似的关联（P < 0.00001，I = 0%），但在白种人中未观察到（P = 0.34，I = 87%）。
年龄可能是影响癫痫患者剂量调整后VPA浓度的关键协变量。对于携带A1075C AC的儿童，尤其是亚洲儿童，可能建议降低VPA剂量。进一步的研究可以提供高质量的证据来证实VPA药代动力学与A1075C多态性之间的相关性。
