Association of genetic variants in six candidate genes with valproic acid therapy optimization.

  title={Association of genetic variants in six candidate genes with valproic acid therapy optimization.},
  author={Chin-Chuan Hung and Jia-Ling Ho and Wei-Lun Chang and John Jen Tai and Tsung-Jen Hsieh and Yow-Wen Hsieh and H H Liou},
  volume={12 8},
AIMS Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The aim of the study was to investigate whether polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of VPA were associated with the large interindividual variability in dosages and concentrations. METHODS & RESULTS Genetic polymorphisms in six candidate genes were detected in 162 epileptic patients under maintenance with VPA monotherapy and stable seizure control by real-time PCR and PCR… 

Association of genetic variants in UGT1A6 genes and non-genetic variant with valproic acid doses and plasma concentration in Thai epileptic patients

Findings suggested that genetic variants in gene encoding drug metabolizing enzyme and non-genetic factor, drug inducer, could explain in part the inter-individual variability in VPA maintenance dose and blood levels.


UGT1A6 polymorphisms may increase VPA metabolism in Egyptian epileptic children affecting both seizure severity as well as susceptibility to ADR.

Lack of association between valproic acid response and polymorphisms of its metabolism, transport, and receptor genes in children with focal seizures

Selected genetic polymorphisms were not significantly associated with VPA response in children with focal seizures, however, three GABR variants showed potential to be associated with the response to VPA.

Influence of UGT2B7 and UGT1A6 polymorphisms on plasma concentration to dose ratio of valproic acid in Chinese epileptic children

This research indicated that UGT2B7 rs7668258 (C>T) and UGT1A6 rs2070959 (A>G) polymorphisms may be correlated to the normalised plasma concentrations of VPA in Chinese epileptic children.

Effect of CYP2C19 polymorphisms on serum valproic level acid in Chinese Han patients with schizophrenia

The findings of this study suggest that the genetic polymorphisms of CYP2C19 significantly affect the steady-state serum concentrations of valproic acid in Chinese Han population.

Effects of UGT1A, CYP2C9/19 and ABAT polymorphisms on plasma concentration of valproic acid in Chinese epilepsy patients.

Detection of genetic polymorphism in these genes might facilitate an appropriate dose of valproic acid for epileptic patients, and further studies are necessary to underpin these observations.

Effect of Genetic Polymorphisms of CYP2C19 on the Steady-state Serum Concentrations of Valproic Acid in Chinese Han Patients With Schizophrenia

It is suggested that CYP2C19 genotypes play an important role in controlling steady-state serum concentrations of valproic acid in Chinese Han population.

[Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate].

The dosage of sodium valproate for the patients with 552C allele in UGT1A6 should be more than the usual dosage.

Genetic Variants in Microsomal Epoxide Hydrolase Influence Carbamazepine Dosing

This proof-of-principle study suggests that genetic variants in EPHX1 can be used to predict maintenance doses of carbamazepine, a large-scale prospective investigation of genetic influences on drug dosing strategies in epilepsy.

A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose

The hypothesis that a common functional polymorphism in the SCN1A gene influences the clinical use of phenytoin is supported and the utility of using multiple phenotypes in pharmacogenetics studies is demonstrated, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects.

Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.

Evidence is provided of a drug target polymorphism associated with the clinical use of AEDs and set the stage for a prospective evaluation of how pharmacogenetic diagnostics can be used to improve dosing decisions in the use of phenytoin and carbamazepine.

[Effect of UGTIA6 A541G genetic polymorphism on the metabolism of valproic acid in Han epileptic children from Henan].

UGT1A6 A541G gene polymorphism does not influence serum concentrations of valproic acid in Han epileptic children and it is concluded that individual differences in serum concentrations in these children may be attributed to many factors.

[An association between the FABP2 gene polymorphism and efficacy of valproates].

It has been shown that the 163G>A (Ala54Thr) polymorphism exerts an influence on effective dose of the valproic acid but not of topiramate.

Sequence variability and candidate gene analysis in two cancer patients with complex clinical outcomes during morphine therapy.

Genetic differences in two morphine-related gene sequences, UDP-glucuronosyltransferase 2B7 (UGT2B7) and mu opioid receptors (MOR1), in two cancer patients whose clinical responses to morphine were very different are presented.

Pharmacokinetic and Pharmacodynamic Interaction of Lorazepam and Valproic Acid in Relation to UGT2B7 Genetic Polymorphism in Healthy Subjects

It is suggested that the UGT2B7 genotype probably affects lorazepam–valproate pharmacodynamic interaction, especially in subjects who have homovariant genotypes of UGT3B7 and UGT1B15, although the effects on the pharmacokinetics are less significant.

Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes.

Allelic variants of UGT2B7, CYP2C8, and ABCC2, which may predispose to the formation and accumulation of reactive diclofenac metabolites are associated withdicl ofenac hepatotoxicity.