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

• Published in: PloS one Vol. 10; no. 4; p. e0125656
• Main Authors: Ni, Guanzhong, Qin, Jiaming, Li, Hongliang, Chen, Ziyi, Zhou, Yafang, Fang, Ziyan, Chen, Yishu, Zhou, Jueqian, Huang, Min, Zhou, Liemin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.04.2015; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Anticonvulsants; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Antiepileptic agents; Atherosclerosis; Blood; Blood diseases; Carbon; Care and treatment; Case-Control Studies; Cross-Sectional Studies; Cyanocobalamin; Deoxyribonucleic acid; Disease; DNA; DNA methylation; DNA Methylation - drug effects; Drugs; Epigenetics; Epilepsy; Epilepsy - blood; Epilepsy - drug therapy; Epilepsy - genetics; Female; Folic acid; Folic Acid - blood; Gene expression; Genomes; Health risk assessment; Heterocyclic Compounds - blood; Homocysteine; Homocysteine - blood; Humans; Laboratories; Long Interspersed Nucleotide Elements; Male; Metabolism; Methylation; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; Neurology; Nutrients; Patients; Pharmaceutical sciences; Pharmacology; Physiological aspects; Pregnancy; Triazines - pharmacology; Triazines - therapeutic use; Valproic Acid - pharmacology; Valproic Acid - therapeutic use; Vitamin B; Vitamin B 12 - blood; Young Adult; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125656

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