Genetic polymorphisms and valproic acid plasma concentration in children with epilepsy on valproic acid monotherapy. (October 2017)

• Record Type: Journal Article
• Authors: Mei, Shenghui; Feng, Weixing; Zhu, Leting; Yu, Yazhen; Yang, Weili; Gao, Baoqin; Wu, Xiaojuan; Zhao, Zhigang; Fang, Fang
• Is Part Of: Seizure. Volume 51(2017)
• Page Start: 22
• Page End: 26
• Publication Date: 2017-10
• Subjects: VPA valproic acid -- FABP2 fatty acid binding protein 2 -- UGT1A6 uridine diphosphate glucuronosyltransferase family 1 member A6 -- UGT2B7 uridine diphosphate glucuronosyltransferase family 2 member B7 -- CYP2C9 cytochrome P450 family 2 subfamily C member 9 -- CYP2A6 cytochrome P450 family 2 subfamily A member 6 -- CYP2B6 cytochrome P450 family 2 subfamily B member 6 -- GABA gamma-aminobutyric acid -- CDRV concentration to dose ratio of valproic acid -- lnCDRV logarithmic transformed CDRV -- MAF minor allele frequency -- HWE Hardy-Weinberg equilibrium -- BETA regression coefficients -- STAT coefficient T-statistic -- UGT1A3/4/5/6/7/8/9/10 uridine diphosphate glucuronosyltransferase family 1 member A 3/4/5/6/7/8/9/10 -- CYP cytochrome P450 -- CYP2C19 cytochrome P450 family 2 subfamily C member 19; Valproic acid -- Epilepsy -- Children -- Concentration to dose ratio -- Polymorphisms -- Pharmacogenomics -- rs28898617; Epilepsy -- Periodicals; Epilepsy -- Periodicals; Seizures -- Periodicals; Épilepsie -- Périodiques; Electronic journals; Electronic journals; 616.853
• DOI: 10.1016/j.seizure.2017.07.005
• Languages: English
• ISSNs: 1059-1311

Abstract

Highlights: rs28898617 was associated with lnCDRV in children on valproic acid monotherapy. The rest 47 variants were not associated with lnCDRV. rs28898617 may be helpful for dose adjustment in children with epilepsy. 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.