Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Neurology, Hamadan University of Medical Sciences, Hamadan, Iran.
J Mol Neurosci. 2018 Apr;64(4):551-558. doi: 10.1007/s12031-018-1059-5. Epub 2018 Mar 16.
Vitamin D deficiency has been detected in epileptic patients. Vitamin D participates in neuroprotection, brain cell proliferation, and differentiation. Consequently, vitamin D supplementation has been suggested as an alternative treatment in epileptic patients. We aimed at assessment of vitamin D signaling pathway in epileptic patients. In the present study, we evaluated vitamin D serum concentration as well as expression of vitamin D receptor (VDR) gene and genes encoding for vitamin D activating enzyme 1-alpha-hydroxylase (CYP27B1) and deactivating enzyme 24-hyroxylase (CYP24A1) in epileptic patients compared with healthy individuals. We found significant lower levels of vitamin D in epileptic patients compared with healthy subjects. Expression analyses showed significant downregulation of VDR expression in peripheral blood of epileptic patients compared with healthy subjects (relative expression (REx) = 0.16, P < 0.001). However, there was no significant difference in CYP24A1 expression between epileptic patients and normal subjects. CYP27B1 expression analysis showed significant upregulation in male patients aged between 30 and 40 (REx = 5.43, P = 0.013). After using two-way ANCOVA for adjusting the effects of sex and age, there was a statistically significant difference in the VDR expression values between patient and control groups (P < 0.001). Spearman's correlation analysis showed no significant correlation between genes expression levels and patients' age or vitamin D serum concentrations. However, we found significant correlations between VDR expression levels and CYP24A1/ CYP27B1 expression levels in epileptic patients (r = 0.435 and P < 0.001; r = 0.26 and P = 0.02 respectively). There was also a significant correlation between the expression levels of CYP24A1 and CYP27B1 (r = 0.349 and P = 0.001). Our study shows a possible role for VDR in the pathogenesis of epilepsy.
维生素 D 缺乏症已在癫痫患者中被发现。维生素 D 参与神经保护、脑细胞增殖和分化。因此，维生素 D 补充已被提议作为癫痫患者的一种替代治疗方法。我们旨在评估癫痫患者的维生素 D 信号通路。在本研究中，我们评估了癫痫患者与健康个体相比的维生素 D 血清浓度以及维生素 D 受体 (VDR) 基因和编码维生素 D 激活酶 1-α-羟化酶 (CYP27B1) 和失活酶 24-羟化酶 (CYP24A1) 的基因表达。我们发现癫痫患者的维生素 D 水平明显低于健康受试者。表达分析显示，与健康受试者相比，癫痫患者外周血中的 VDR 表达显著下调（相对表达 (REx) = 0.16，P < 0.001）。然而，癫痫患者和正常受试者之间 CYP24A1 表达无显著差异。CYP27B1 表达分析显示，30 至 40 岁男性患者表达显著上调（REx = 5.43，P = 0.013）。在用双因素方差分析调整性别和年龄的影响后，患者组和对照组之间的 VDR 表达值存在统计学差异（P < 0.001）。Spearman 相关分析显示，基因表达水平与患者年龄或维生素 D 血清浓度之间无显著相关性。然而，我们发现癫痫患者 VDR 表达水平与 CYP24A1/CYP27B1 表达水平之间存在显著相关性（r = 0.435 和 P < 0.001；r = 0.26 和 P = 0.02）。CYP24A1 和 CYP27B1 之间的表达水平也存在显著相关性（r = 0.349 和 P = 0.001）。我们的研究表明 VDR 在癫痫发病机制中可能发挥作用。
