Genetic polymorphisms and valproic acid plasma concentration in children with epilepsy on valproic acid monotherapy

Abstract

Purpose The aim of the study is to evaluate the association between genetic polymorphisms and valproic acid (VPA) concentration to dose ratio in children with epilepsy on VPA monotherapy. Methods A total of 137 children, aged 3.5–18 years, (89 males and 48 females) with epilepsy on sustained-release VPA monotherapy were enrolled. Trough plasma concentrations of VPA at steady-state were measured using an AXSYM automatic immunity analyzer. The values were divided by body weight and total daily dose to calculate concentration to dose ratio of VPA (CDRV). Forty-eight single nucleotide polymorphisms involved in the pharmacokinetics of VPA were identified by MassARRAY system. The logarithmic transformed CDRV (lnCDRV) was normally distributed, and PLINK software was used to evaluate the association between genetic polymorphisms and lnCDRV using linear regression adjusted for gender and seizure type. Results rs28898617 (UGT1A3/4/5/6/7/8/9/10, BETA = 0.32, P = 0.0089) was significantly associated with higher lnCDRV. No other associations were found. Conclusions In pediatric patients taking VPA monotherapy, rs28898617 was associated with a higher normalized VPA plasma concentration. Further studies are warranted to confirm the results.