细胞色素P450 2C9基因多态性与癫痫易感性及其与丙戊酸血清浓度相关性  

Association of cytochrome P450 2C9 genetic polymorphisms with susceptibility to epilepsy and serum concentration of valproate acid

作　　者：尹胜菊[1,2] 许新升 刘新风 程世亮[1] 王翠花 

机构地区：[1]山东省交通医院检验科,济南250031 [2]济南齐鲁医学检验所,济南250031 [3]淄博昌国医院检验科,山东淄博255000

出　　处：《中国临床药理学杂志》2017年第19期1906-1908,共3页The Chinese Journal of Clinical Pharmacology

基　　金：山东省医药卫生科技发展计划基金资助项目(2015WS0261)

摘　　要：目的考察细胞色素P450 2C9*3(CYP2C9*3)(1075A>C)基因多态性与癫痫易感性及其与丙戊酸钠(VPA)血清浓度的相关性。方法收集245名健康志愿者和191例癫痫患者的外周血,提取DNA。用Sequenom Mass Array方法检测CYP2C9*3基因型,用荧光偏振免疫分析法测定VPA稳态血清浓度。结果癫痫患者和健康志愿者的CYP2C9*3等位基因频率分别为4.45%和2.04%,差异有统计学意义(P<0.05)。C等位基因频率的优势比为2.23,C等位基因显著增加癫痫的发病风险(P<0.05)。CYP2C9*1/*1基因型组和CYP2C9*1/*3基因型组癫痫患者的稳态VPA浓度分别为(55.90±21.11)和(67.75±21.36)μg·m L-1,差异有统计学意义(P<0.05)。结论 CYP2C9*3可显著增加癫痫的发病风险,C等位基因是癫痫的易感等位基因,且CYP2C9*3基因多态性可影响VPA稳态血清浓度。Objective To investigate the association of cytochrome P4502C9（ CYP2C9＊ 3）（ 1075 A C） gene polymorphisms with the susceptibility to epilepsy and the serum concentration of valproate acid（ VPA）.Methods DNA was extracted from peripheral blood of 245 healthy subjects and 191 patients with epilepsy. The CYP2C9＊ 3 genotype was detected by sequenom mass array method. The steady-state serum concentration of VPA was determined by fluorescence polarization immunoassay.Results The frequencies of CYP2C9＊ 3 alleles in patients with epilepsy and healthy subjects were 4. 45% and 2. 04%,respectively,and the difference was statistically significant（ P〈0. 05）. The C allele frequency odds ratio was 2. 23, C allele increased the risk of epilepsy（ P〈0. 05）. The steady-state VPA concentration in patients with CYP2C9＊ 1/＊ 1 genotype and patients with CYP2C9 ＊ 1/＊ 3 genotype were（ 55. 90 ± 21. 11） and（ 67. 75 ± 21. 36） μg·m L^-1,respectively,and the difference was statistically significant（ P〈0. 05）. Conclusion CYP2C9 ＊ 3 significantly increases the risk to develop epilepsy and C allele is a susceptible allele for epilepsy. CYP2C9＊ 3 polymorphisms are associated with serum concentrations of VPA in epilepsy patients.

关 键 词：癫痫 细胞色素P4502C9 丙戊酸 血清浓度 

分 类 号：R971.6[医药卫生—药品]