丙戊酸药物浓度与CYP286基因多态性的相关性研究

目的:探讨丙戊酸(VPA)药物浓度与细胞色素P4502B6(CYP2B6)基因多态性的关系。方法:选择符合入选条件的癫患者72例,提取外周血DNA,应用聚合酶链反应和限制性核酸内切酶方法分析患者的CYP2B6基因型及等位基因;应用荧光偏振免疫法测定患者VPA的血药浓度。结果:72例癫患者中CYP2B6基因型为*1/*1为39例(54.2%),*1/*6为29例(40.3%),*6/*6为4例(5.5%),根据基因型将患者分为两组,A组(CYP2B6*1/*1)和B组(CYP2B6*1/*6或CYP2B6*6/*6)。B组患者VPA的标准血药浓度平均值较A组高,且差异有统计学意义(P<0.05)。结论:CYP2B6是VPA的代谢酶,CYP2B6基因多态性可影响VPA的血药浓度,对含有CYP2B6*6等位基因的患者应用VPA时,其血药浓度高,提示对VPA药物代谢有影响。

Association Study Between Valproic Acid Plasma Concentration and CYP2B6 Gene Polymorphism

Aim:To investigate the association between valproic acid(VAP)plasma concentration and CYP2B6 gene polymorphisms for better individualized medication on the basis of different genotypes of CYP2B6.Methods:A total of 72 patients receiving valproic acid after more than 5 half-time periods were recruited.The genotypes of CYP2B6 of the patients were detected by polymerase chain reaction and digestion with restriction enzyme to examine the alleles CYP2B6*1 and CYP2B6*6.Fluorescence polarization immunoassay was used to measure the serum concentration of valproic acid which was standardized by dosage and body weight.Results:Of the 72 cases,39(54.2%)were wild genotypes,29(40.3%)were CYP2B6*1/*6 genotypes and 4(5.5%)was CYP2B6*6/*6 genotype.According to the genotypes of CYP2B6 the patients were divided into two groups:one was group A(CYP2B6*1/*1)and the other was group B(CYP2B6*1/*6 or *6/*6).The mean value of the serum concentration of valproic acid of the patients in group A was higher than that in group B,which had statistical significance(P<0.05).Conclusion:Valproic acid is metabolized via CYP2B6.The genetic polymorphisms of CYP2B6 affect the VPA plasma concentration.When the patients with CYP2B6*6 allele took VPA,VPA plasma concentration was high and indicated that the genetic polymorphisms of CYP2B6 had an effect to VPA drug metabolism.