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Therapies
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le vendredi 30 août 2019
Doi : 10.1016/j.therap.2019.07.003
Received : 18 June 2018 ;  accepted : 22 July 2019
Association of UGT2B7 and CaMK4 with response of valproic acid in Chinese children with epilepsy
 

Yan Wang a, b, Zhiping Li a,
a Department of pharmacy, children's hospital of Fudan university, Shanghai 201102, China 
b College of pharmacy, Hainan medical university, Haikou 571199, China 

Corresponding author.
Summary
Aim of the study

Valproic acid (VPA) is a widely used antiepileptic drug for epilepsy. However, approximately 30% of patients with epilepsy do not respond to this therapy even when it was appropriately used. In order to explore the potential genetic factors related to the VPA response, this pharmacogenetics study was conducted.

Methods

A total of one hundred and fifty-seven Chinese children with epilepsy who were administered with by VPA for at least one year were enrolled. Thirteen single-nucleotide polymorphisms (SNPs) located in eight genes involving targets and metabolic enzymes of VPA were genotyped. The frequencies of these polymorphisms and the effect of genotypes on the efficacy of VPA were analyzed.

Results

The frequencies of two SNPs, rs7668258 (uridine diphosphate glucuronosyltransferase-2B7, UGT2B7 ) and rs306104 (calmodulin-kinase 4, CaMK4 ) were associated with VPA responses. However, no association was found for the other SNPs. Furthermore, the polymorphism of UGT2B7 influenced the adjusted concentration (AC) in the responders rather than in the non-responders.

Conclusion

Two SNPs (UGT2B7 and CaMK4 ) were associated with VPA response, which may explain the pharmacological mechanism of VPA resistance to some extent.

The full text of this article is available in PDF format.

Keywords : UGT2B7 , CaMK4 , Valproic acid, Efficacy, Resistance




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