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 vitamin B12), 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 homocysteine and vitaminB12 levels and lower folate levels relative to controls (P = 0.018, P = 0.003, P < 0.001 respectively), the methylation level of the MTHFR amplicon was significantly lower in the VPA group compared with those in the controls (P = 0.043). VPA-treated epileptic patients carrying the T-allele of methylenetetrahydrofolate reductase (MTHFR) c.677C>T showed higher serum Hcy levels than those observed in the 677CC group (P < 0.01). Epileptic patients who carried G-allele of methionine synthase (MTR) c.2756A>G 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.
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Authors | Guanzhong Ni, Jiaming Qin, Ziyi Chen, Hongliang Li, Jueqian Zhou, Min Huang, Liemin Zhou |
Journal | Clinical nutrition (Edinburgh, Scotland)
(Clin Nutr)
Vol. 37
Issue 1
Pg. 308-312
(02 2018)
ISSN: 1532-1983 [Electronic] England |
PMID | 28161091
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. |
Chemical References |
- Anticonvulsants
- Valproic Acid
- Methyltransferases
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Topics |
- Adolescent
- Adult
- Anticonvulsants
(therapeutic use)
- Case-Control Studies
- DNA Methylation
(genetics)
- Epilepsy
(drug therapy, epidemiology, genetics)
- Female
- Humans
- Leukocytes
(chemistry)
- Male
- Methyltransferases
(genetics, metabolism)
- Polymorphism, Single Nucleotide
(genetics)
- Valproic Acid
(therapeutic use)
- Young Adult
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