CYP2C9与CYP2C19基因多态性与癫痫患者丙戊酸血药浓度关系研究  

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

作　　者：谭喜莹[1] 张宇[2] 王淑云[1] 邱召娟[1] 

机构地区：[1]江苏省中医院药剂科,南京210029 [2]南京医科大学药学院,南京210029

出　　处：《药学与临床研究》2011年第2期123-126,共4页Pharmaceutical and Clinical Research

摘　　要：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CYP2C9*1*1合并CYP2C19*1*1的野生型纯合子强代谢者(EM),基因型为CYP2C9*1*3或CYP2C19*1*2或CYP2C19*1*3的杂合中等代谢者(IM),基因型为CYP2C9*3*3或CYP2C9*1*3合并CYP2C19*1*3或CYP2C19*2*2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。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.Results： Forty patients with CYP2C9 and/or CYP2C19 allele variants were classified into 3 groups： extensive metabolizer（EM） homozygous for CYP2C19＊1＊1 combined with CYP2C9＊1＊1 alleles,intermediate metabolizer（IM） heterozygous for CYP2C9＊1＊3 or CYP2C19＊1＊2 or CYP2C19＊1＊3 and poor metabolizer（PM） with the genotype of CYP2C9＊3＊3 or CYP2C9＊1＊3 combined with CYP2C19＊1＊3 or CYP2C19＊2＊2.The genotype distribution rates of EM,IM,and PM were 47.5%,25% and 27.5% respectively.The VPA serum concentration of the PM group was significantly higher than that of the EM group（P〈0.05）.Conclusion： VPA is metabolized via CYP2C9 and CYP2C19.The VPA serum concentration of the PM is significantly higher.Genotyping helps predict the clinical response to VPA administration.

关 键 词：癫痫 丙戊酸 基因多态性 细胞色素氧化酶 

分 类 号：R969.1[医药卫生—药理学]