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


CONCLUSIONS
Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Guanzhong
G
Ni
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Jiaming
J
Qin
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Hongliang
H
Li
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Ziyi
Z
Chen
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Yafang
Y
Zhou
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Ziyan
Z
Fang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Yishu
Y
Chen
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Jueqian
J
Zhou
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Min
M
Huang
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Liemin
L
Zhou
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000187:drug effects*; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood; D006571:Heterocyclic Compounds / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D000077213:Lamotrigine; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
D000927:Anticonvulsants; D006571:Heterocyclic Compounds; D014227:Triazines; D006710:Homocysteine; D014635:Valproic Acid; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12; D000077213:Lamotrigine