CYP450酶基因多态性对丙戊酸血药浓度的影响  

Effects of CYP450 enzymes polymorphisms on plasma Valproic acid concentration

作　　者：张媞[1] 徐善森 刘长文[2] 杨帆[1] 陈亚南[1] 肇丽梅[1] 

机构地区：[1]中国医科大学附属盛京医院药学部,辽宁沈阳110004 [2]东北制药集团沈阳第一制药有限公司,辽宁沈阳110869

出　　处：《中国生化药物杂志》2016年第2期1-4,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然基金(81302857);辽宁省自然科学基金(2013021079)

摘　　要：目的探究CYP2C9、CYP2A6和CYP2B6基因多态性对单用丙戊酸(Valproic acid,VPA)治疗的癫痫患儿血药浓度的影响。方法收集单用VPA治疗的癫痫患儿400例,记录患儿的年龄、性别、体质量、日服药剂量等基本信息;应用荧光偏振免疫法(fluorescence polarigation immunoassay,FPIA)测定VPA血药浓度;采用聚合酶链式反应(PCR)扩增目的片段,分别采用直接测序法、巢式PCR法和质谱法检测CYP2C9*3、CYP2A6*4和CYP2B6*6位点的基因型。应用单因素方差分析(ANOVA)考查基因多态性对VPA血药浓度的影响。结果 400例癫痫患儿CYP2C9*3、CYP2A6*4、CYP2B6*6的等位基因频率分别为2.75%、6.50%、23.00%,其中CYP2C9*3和CYP2A6*4基因多态性可以显著升高VPA标准化血药浓度(concentration dose ratio,CDRVPA)(P=0.024;P=0.000),但CYP2B6*6基因多态性对CDRVPA的影响差异无统计学意义(P=0.95)。结论 CYP2C9*3和CYP2A6*4等位基因多态性均能影响CDRVPA,因此CYP2C9*3和(或)CYP2A6*4等位基因携带的患儿VPA使用剂量应低于常规剂量,以避免发生不良反应。Objective To investigate the effects of genetic polymorphisms（ CYP2C9, CYP2A6 and CYP2B6） on the concentration of Valproic acid in the epileptic children. Methods A total of 400 cases were collected in our study. PCR, nest-PCR and direct sequencing were applied to identify the frequency of CYP2C9 ＊ 3 ,CYP2A6 ＊ 4 and CYP2B6 ＊ 6. One-way ANOVA was used to analyze the influence of the SNPs on CDRvpA. Results The frequencies of allele CYP2C9 ＊ 3, CYP2A6 ＊ 4, CYP2B6 ＊ 6 were 2. 75% ,6. 50% ,23.00% respectively. The CDRvPA in epileptic children with allele CYP2C9 ＊ 3 and CYP2A6 ＊ 4 were significantly higer than that in children with the wild type （ P = 0. 024 ; P = 0. 000）, there was no significant difference between the epileptic children with allele CYP2B6 ＊ 6 and wild type（P =0. 095）. Conclusion The CDRvPAis affected by the SNPs of CYP2C9 ＊ 3 and CYP2A6 ＊ 4. The dosage of VPA in epileptic ehildren with alleles CYP2C9 ＊ 3 and CYP2A6 ＊ 4 should be lower in case of adverse reaction.

关 键 词：丙戊酸 CYP450酶 基因多态性 血药浓度 

分 类 号：R969[医药卫生—药理学]