PloS one · 2015
Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy.
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Ni Guanzhong, Qin Jiaming, Li Hongliang, Chen Ziyi, Zhou Yafang, Fang Ziyan, Chen Yishu, Zhou Jueqian, Huang Min, Zhou Liemin
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAdultAnticonvulsantsCase-Control StudiesCross-Sectional StudiesDNA MethylationEpilepsyFemaleFolic AcidHeterocyclic CompoundsHomocysteineHumansLamotrigineLong Interspersed Nucleotide ElementsMaleMethylenetetrahydrofolate Reductase (NADPH2)Middle AgedTriazinesValproic AcidVitamin B 12Young Adult