The Effect Of CYP2A6 Genetic Polymorphisms On The Serum Concentration Of Sodium Valproate

Objective: To investigate the effect of cytochrome P450 2A6 (CYP2A6) genetic polymorphisms on the serum concentration of sodium valproate for better individualized medication on the basis of different genotypes of CYP2A6.Methods: A total of 98 patients (male 51,female 47) receiving sodium valproate after more than 5 half-time periods were recruited. The genotypes of CYP2A6 of the patients were detected by nested-primer polymerase chain reaction (PCR) to examine the alleles CYP2A6*1 and CYP2A6*4. Fluorescence polarization immunoassay (FPIA) was used to measure the serum concentration of sodium valproate which was standardized by dosage and body weight.Result: Of the 98 cases, 73 (74.5%) were wild genotypes, 24 (24.5%) were CYP246*1/*4 genotypes and 1(1.0%) was CYP2A6*4I*4 genotype. The alleles frequencies of the CYP2A6*1 and CYP2A6*4 were 86.7% and 13.3% respectively. According to the genotypes of CYP2A6 the patients were divided into two groups, one was group A (CYP2A6*1/*1) and the other was group B (CYP2A6*l/*4 or *4/*4). The mean value of the serum concentration of sodium valproate of the patients in group A was higher than that in group B, which had statistical significance (P<0.05). The mean value of the serum concentration of sodium valproate in patients with CYP2A6*l/*4 genotypes was higher than that in patients with CYP2A6*1/*1 genotypes, which had statistical significance (P<0.05) as well. Conclusions: Sodium valproate is metabolized via CYP2A6.The genetic polymorphisms of CYP2A6 affect the serum concentration of sodium valproate. The dosage of sodium valproate in patients with CYP2A6*4 allele should be lower than usual to prevent the adverse effect and wasting the medicine resource.