Ni Guanzhong, Qin Jiaming, Li Hongliang, Chen Ziyi, Zhou Yafang, Fang Ziyan, Chen Yishu, Zhou Jueqian, Huang Min, Zhou Liemin
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
PLoS One. 2015 Apr 27;10(4):e0125656. doi: 10.1371/journal.pone.0125656. eCollection 2015.
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.
本研究旨在比较接受抗癫痫药物（AEDs）治疗的癫痫患者与健康对照者的一碳代谢（OCM）营养素（如叶酸、同型半胱氨酸和维生素B12）血清水平及外周血DNA甲基化情况。
在这项横断面研究中，纳入了60例接受丙戊酸（VPA）（n = 30）或拉莫三嗪（LTG）（n = 30）单药治疗的癫痫患者。30名年龄和性别匹配的健康受试者作为对照。检测OCM营养素的血清浓度及外周血DNA甲基化状态。
与对照组相比，VPA组的同型半胱氨酸血清水平较高（p<0.05）。LTG组未观察到同型半胱氨酸浓度有差异。与对照组相比，接受VPA或LTG治疗的患者血清叶酸水平显著降低（p<0.001）。AED单药治疗组与健康对照组外周血中长散在核苷酸元件-1（LINE-1）的甲基化水平无显著差异。癫痫患者接受AED治疗与对照组之间观察到亚甲基四氢叶酸还原酶（MTHFR）扩增子甲基化水平存在差异（p<0.01）。还观察到血清叶酸水平与外周血MTHFR扩增子甲基化状态之间呈正相关（r = 0.25，p = 0.023）。
我们的研究结果表明，AED单药治疗对OCM的影响可能会诱导特定区域的DNA低甲基化。
