摘要
目的探讨丙戊酸(VPA)药物浓度与细胞色素P450 2B6(CYP2B6)基因多态性的关系,以便根据患者的基因型指导临床对癫痫患者进行个体化用药。
方法选择单药服用丙戊酸且无肝肾功能异常的癫痫患者72例,提取其外周血中的DNA,应用聚合酶链反应(PCR)方法和限制性内切核酸酶酶切的方法分析患者的CYP2B6基因型及等位基因CYP2B6*1及CYP2B6*6频率;同时应用荧光偏振免疫法(FPIA)测定不同基因型患者丙戊酸的血药浓度。
结果72例癫痫患者(男性32名,女性40名)中CYP2B6基因型中*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组患者丙戊酸的标准血药浓度平均值较A组的平均值高,且差异有统计学意义(P＜0.05)。
结论CYP2B6是丙戊酸的代谢酶,CYP2B6基因多态性可影响丙戊酸的血药浓度,对含有CYP2B6*6等位基因的患者应用丙戊酸时应较常规降低用量,以减少不良反应的发生和避免药物资源的浪费。
Objective: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(male 32,female 40) 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(PCR) and digestion with restriction enzyme to examine the alleles CYP2B6~*1 and CYP2B6~*6.Fluorescence polarization immunoassay (FPIA) was used to measure the serum concentration of valproic acid which was standardized by dosage and body weight.
Result: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).
Conclusions:Valproic acid is metabolized via CYP2B6.The genetic polymorphisms of CYP2B6 affect the VPA plasma concentration.The dosage of valproic acid in patients with CYP2B6~*6 allele should be lower than usual to prevent the adverse effect and wasting the medicine resource.
引文
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