Associations between genetic variation in one-carbon metabolism and leukocyte DNA methylation in valproate-treated patients with epilepsy ( YCLNU-D-16-00558R2 )

Abstract Background Valproate (VPA) as a first-line antiepileptic drug is useful for the most types of epileptic seizure treatment. Previous studies observed that VPA influenced one-carbon metabolism (OCM), consequently, DNA methylation. However, other individual genetic variations, as well as VPA, modify DNA methylation. Objective In this study, we investigated associations between genetic variations in OCM and leukocyte DNA methylation in VPA-treated patients with epilepsy. Methods This was a cross-sectional study of 101 epileptic patients who underwent VPA monotherapy and 68 healthy controls. All subjects were measured OCM-related nutrients (folate, homocysteine and vitaminB12), and DNA methylation of specific regions were analyzed. Furthermore, we examined the associations between genetic variations in OCM and DNA methylation levels in epileptic patients. Results VPA-treated patients with epilepsy exhibited both higher serum Hcy and vitaminB12 levels and lower FA levels relative to controls ( P =0.018, P =0.003, P T showed higher serum Hcy levels than those observed in the 677CC group (pG showed significantly lower MTHFR amplicon methylation levels compared to carriers of the wild-type MTR 2756AA genotype (p=0.028). Conclusion Our study provided evidence that the MTR c.2756A>G polymorphism is associated with MTHFR amplicon hypomethylation in VPA-treated patients with epilepsy.