Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy.

Abstract

PURPOSE:

The aim of this study was to compare the serum levels of one-carbon metabolism (OCM) nutrients (e.g., folate, homocysteine and vitamin B12) and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs) and in healthy controls.

METHODS:

In this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA) (n = 30) or lamotrigine (LTG) (n = 30) monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.

RESULTS:

Compared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05). No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001). The level of methylation of long interspersed nucleotide element-1 (LINE-1) in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR) amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01). A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023).

CONCLUSION:

Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.

• Authors: Guanzhong Ni, Jiaming Qin, Hongliang Li, Ziyi Chen, Yafang Zhou, Ziyan Fang, Yishu Chen, Jueqian Zhou, Min Huang, Liemin Zhou
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0125656 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25915064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Heterocyclic Compounds
• Triazines
• Homocysteine
• Valproic Acid
• Folic Acid
• MTHFR protein, human
• Methylenetetrahydrofolate Reductase (NADPH2)
• Vitamin B 12
• Lamotrigine

Topics

• Adolescent
• Adult
• Anticonvulsants (pharmacology, therapeutic use)
• Case-Control Studies
• Cross-Sectional Studies
• DNA Methylation (drug effects)
• Epilepsy (blood, drug therapy, genetics)
• Female
• Folic Acid (blood)
• Heterocyclic Compounds (blood)
• Homocysteine (blood)
• Humans
• Lamotrigine
• Long Interspersed Nucleotide Elements
• Male
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Middle Aged
• Triazines (pharmacology, therapeutic use)
• Valproic Acid (pharmacology, therapeutic use)
• Vitamin B 12 (blood)
• Young Adult