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

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(P0.05).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.