CYP2C9与CYP2C19基因多态性与癫痫患者丙戊酸血药浓度关系研究

目的:探讨细胞色素氧化酶P450 2C9(CYP2C9)和CYP2C19基因型对癫痫患者丙戊酸血药浓度的影响.方法:对40例癫痫患者应用限制性酶切片段多态性技术分析中国人常见的1个CYP2C9和2个CYP2C19等位基因变异,应用荧光偏振免疫法测定患者丙戊酸的血药浓度,在进行标准化以排除剂量和体重对血药浓度的影响后,分析CYP2C9、CYP2C19基因型和丙戊酸血药浓度的关系.结果:根据携带CYP2C9和CYP2C19突变等位基因的数量,将患者分为基因型CYP2C911合并CYP2C1911的野生型纯合子强代谢者(EM).基因型为CYP2C913或CYP2C1912或CYP2C1913的杂合中等代谢者(IM),基因型为CYP2C933或CYP2C913合并CYP2C1913或CYP2C1922的突变型纯合子弱代谢者(PM).三组频率分别为47.5%、25%和27.5%.并且突变基因携带数量与标准化血药浓度呈正相关.PM患者服用等剂量丙戊酸时血药浓度比EM患者高(P<0.05).结论:丙戊酸代谢受CYP2C9和CYP2C19基因调控.检测患者CYP2C9和CYP2C19基因型可以预测患者药物浓度,有利于临床选择适宜的丙戊酸初始剂量.

Association between Genetic Polymorphisms of CYP2C9 and CYP2C19 and Serum Valproate Concentration

Objective: To investigate the relationship between the genetic polymorphism of cytochrome P450 CYP2C9 and CYP2C19 and the serum concentration of valproate(VPA) in patients with epilepsy.Methods: The peripheral blood samples of 40 patients with epilepsy aged 8~79 were collected to undergo PCR.PCR-RFLP method was used to examine the 2 common CYP2C19 allele variants and one CYP2C9 allele.Fluorescence polarization immunoassay was used to measure the VPA serum concentration standardized by dosage and body weight...