Association Study Between Valproic Acid Plasma Concentration And CYP2B6 Gene Polymorphism

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.