Associations between genetic variation in one-carbon metabolism and leukocyte DNA methylation in valproate-treated patients with epilepsy
Associations between genetic variation in one-carbon metabolism and leukocyte DNA methylation in valproate-treated patients with epilepsy
复制标题
接受丙戊酸治疗的癫痫患者一碳代谢遗传变异与白细胞 DNA 甲基化之间的关联。
DOI：
10.1016/j.clnu.2017.01.004
复制
发表时间：
2018-02-01
影响因子：
6.3
通讯作者：
Zhou, Liemin
中科院分区：
文献类型：
--
作者：
Ni, Guanzhong;Qin, Jiaming;Zhou, Liemin
背景：丙戊酸盐（VPA）作为一线抗癫痫药物，可用于治疗大多数类型的癫痫发作。以往的研究观察到VPA影响一碳代谢（OCM），从而影响DNA甲基化。然而，其他个人的遗传变异，以及VPA，修改DNA methylation.Objective：在这项研究中，我们调查了在OCM和白细胞DNA甲基化VPA治疗patients with epilepsy.Methods：这是一个横断面研究101癫痫患者接受VPA单药治疗和68名健康对照的遗传变异之间的关联。所有受试者均检测了OCM相关营养素（叶酸、同型半胱氨酸和维生素B12），并分析了特定区域的DNA甲基化。此外，我们研究了癫痫患者中OCM的遗传变异与DNA甲基化水平之间的关系。与对照组相比，VPA治疗的癫痫患者血清同型半胱氨酸和维生素B12水平较高，叶酸水平较低（P = 0.018，P = 0.003，P < 0.001），VPA组MTHFR扩增子甲基化水平显著低于对照组（P = 0.043）。携带亚甲基四氢叶酸还原酶（MTHFR）c.677C>T等位基因的VPA治疗癫痫患者血清Hcy水平高于677CC组（P < 0.01）。结论：MTR c.2756A>G多态性与VPA治疗癫痫患者MTHFR扩增子甲基化水平相关，MTR c.2756A> G等位基因携带者MTHFR扩增子甲基化水平显著低于MTR 2756AA野生型携带者（P = 0.028）。(C)2017 Elsevier Ltd和欧洲临床营养与代谢学会。All rights reserved.
Background: Valproate (VPA) as a first-line antiepileptic drug is useful for the most types of epileptic seizure treatment. Previous studies observed that VPA influenced one-carbon metabolism (OCM), consequently, DNA methylation. However, other individual genetic variations, as well as VPA, modify DNA methylation.Objective: In this study, we investigated associations between genetic variations in OCM and leukocyte DNA methylation in VPA-treated patients with epilepsy.Methods: This was a cross-sectional study of 101 epileptic patients who underwent VPA monotherapy and 68 healthy controls. All subjects were measured OCM-related nutrients (folate, homocysteine and vitamin B12), and DNA methylation of specific regions were analyzed. Furthermore, we examined the associations between genetic variations in OCM and DNA methylation levels in epileptic patients.Results: VPA-treated patients with epilepsy exhibited both higher serum homocysteine and vitaminB12 levels and lower folate levels relative to controls (P = 0.018, P = 0.003, P < 0.001 respectively), the methylation level of the MTHFR amplicon was significantly lower in the VPA group compared with those in the controls (P = 0.043). VPA-treated epileptic patients carrying the T-allele of methylenetetrahydrofolate reductase (MTHFR) c.677C>T showed higher serum Hcy levels than those observed in the 677CC group (P < 0.01). Epileptic patients who carried G-allele of methionine synthase (MTR) c.2756A>G showed significantly lower MTHFR amplicon methylation levels compared to carriers of the wild-type MTR 2756AA genotype (P = 0.028).Conclusion: Our study provided evidence that the MTR c.2756A>G polymorphism is associated with MTHFR amplicon hypomethylation in VPA-treated patients with epilepsy. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.