Wang Ping, Lin Xiao-Qian, Cai Wen-Ke, Xu Gui-Li, Zhou Meng-Di, Yang Mei, He Gong-Hao
Department of Pharmacy, Kunming General Hospital of PLA, 212 Daguan Rd, Kunming, 650032, China.
Kunming Medical University, Kunming, 650032, China.
Eur J Clin Pharmacol. 2018 Apr;74(4):433-442. doi: 10.1007/s00228-017-2395-z. Epub 2017 Dec 14.
Valproic acid (VPA) is one of the most widely used antiepileptic drugs. Recently, increasing evidence suggested that polymorphisms in UGT2B7 gene were associated with VPA pharmacokinetics, but results remained controversial. Therefore, a meta-analysis was performed to derive a more precise evaluation between C802T, C161T, and G211T polymorphisms and plasma concentration of VPA.
The PubMed, EMBASE, and the Cochrane library databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed, and the available data were accumulated. The mean difference (MD) and 95% confidence interval (CI) were applied to assess the strength of the relationship.
A total of 12 studies involving 1996 related East Asia epilepsy patients were assessed. We found that the UGT2B7 G211T polymorphism was associated with adjusted plasma VPA concentration (GG versus TT: P = 0.01, I = 97%; GG versus GT: P < 0.00001, I = 0%). Additionally, we also observed a significantly association between the C161T polymorphism and adjusted plasma VPA concentration (CC versus CT: P = 0.01, I = 77%). Nevertheless, the pooled analysis showed that the C802T polymorphism had no significant effect on adjusted serum concentration of VPA.
The results of this meta-analysis demonstrated that UGT2B7 G211T and C161T polymorphisms were able to affect the pharmacokinetics in epilepsy patients treated with VPA, which provide further evidence for genetic effects of UGT2B7 gene on pharmacokinetics and pharmacodynamics of VPA. Epilepsy patients with these genotypes may be necessary to increase (or decrease) VPA dose to ensure its therapeutic effect.
丙戊酸（VPA）是使用最广泛的抗癫痫药物之一。最近，越来越多的证据表明，UGT2B7基因多态性与VPA药代动力学相关，但结果仍存在争议。因此，进行了一项荟萃分析，以更精确地评估C802T、C161T和G211T多态性与VPA血浆浓度之间的关系。
检索PubMed、EMBASE和Cochrane图书馆数据库中的合格研究。对符合纳入标准的文章进行全面综述，并汇总可用数据。应用平均差（MD）和95%置信区间（CI）评估关系强度。
共评估了12项研究，涉及1996名东亚癫痫患者。我们发现UGT2B7 G211T多态性与调整后的血浆VPA浓度相关（GG与TT：P = 0.01，I² = 97%；GG与GT：P < 0.00001，I² = 0%）。此外，我们还观察到C161T多态性与调整后的血浆VPA浓度之间存在显著关联（CC与CT：P = 0.01，I² = 77%）。然而，汇总分析表明C802T多态性对调整后的VPA血清浓度无显著影响。
这项荟萃分析的结果表明，UGT2B7 G211T和C161T多态性能够影响接受VPA治疗的癫痫患者的药代动力学，这为UGT2B7基因对VPA药代动力学和药效学的遗传效应提供了进一步的证据。具有这些基因型的癫痫患者可能需要增加（或减少）VPA剂量以确保其治疗效果。
