Association of valproic acid-related pharmacodynamics, pharmacokinetic pathways and transporter gene polymorphisms and antiepileptic efficacy in Chinese Patients.

Abstract

Valproic acid(VPA) has great individual differences in clinical efficacy, the study aimed to investigate the effects of VPA-related pharmacogenomics on the antiepileptic efficacy of VPA, so as to provide evidence for clinical rational drug use.The patients were followed up for one year, and the number of seizures within one year was used as the evaluation index of efficacy. The target SNPS were genotyped by SNPscan method.A total of 253 patients with epilepsy treated with valproate monotherapy were enrolled in this study, including 125 patients in the valproate-sensitive group and 128 patients in the valproate-resistant group. χ² test showed that the frequency of C allele of CACNA1H rs3751664 in valproate-sensitive group was significantly higher than that in valproate-resistant group (93.6% vs. 87.5%, P = 0.023), and the difference was still statistically significant after adjusting for confounding factors by logistic regression analysis(P = 0.037). Haplotype analysis showed no association between gene polymorphisms and efficacy of valproic acid.CACNA1C rs1051375 GG and GA genotype patients have a lower risk of drug resistance than AA genotype patients, CACNA1H rs3751664 T allele is a risk factor for VPA monoresistance, while APEH rs3816877 CT genotype patients have a trend of drug resistance during VPA treatment.