Ji Huihui, Wang Yunliang, Liu Guili, Chang Lan, Chen Zhongming, Zhou Dongsheng, Xu Xuting, Cui Wei, Hong Qingxiao, Jiang Liting, Li Jinfeng, Zhou Xiaohui, Li Ying, Guo Zhiping, Zha Qin, Niu Yanfang, Weng Qiuyan, Duan Shiwei, Wang Qinwen
Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Department of Neurology, the 148 Central Hospital of PLA, Zibo, Shandong, China.
PLoS One. 2017 Mar 2;12(3):e0172335. doi: 10.1371/journal.pone.0172335. eCollection 2017.
Aberrant DNA methylation has been observed in the patients with Alzheimer's disease (AD), a common neurodegenerative disorder in the elderly. OPRD1 encodes the delta opioid receptor, a member of the opioid family of G-protein-coupled receptors. In the current study, we compare the DNA methylation levels of OPRD1 promoter CpG sites (CpG1, CpG2, and CpG3) between 51 AD cases and 63 controls using the bisulfite pyrosequencing technology. Our results show that significantly higher CpG3 methylation is found in AD cases than controls. Significant associations are found between several biochemical parameters (including HDL-C and ALP) and CpG3 methylation. Subsequent luciferase reporter gene assay shows that DNA fragment containing the three OPRD1 promoter CpGs is able to regulate gene expression. In summary, our results suggest that OPRD1 promoter hypermethylation is associated with the risk of AD.
在阿尔茨海默病（AD）患者中观察到异常的DNA甲基化，AD是老年人常见的神经退行性疾病。OPRD1编码δ阿片受体，它是G蛋白偶联受体阿片家族的成员。在本研究中，我们使用亚硫酸氢盐焦磷酸测序技术比较了51例AD病例和63例对照之间OPRD1启动子CpG位点（CpG1、CpG2和CpG3）的DNA甲基化水平。我们的结果表明，AD病例中CpG3甲基化水平显著高于对照组。在几个生化参数（包括高密度脂蛋白胆固醇和碱性磷酸酶）与CpG3甲基化之间发现了显著关联。随后进行的荧光素酶报告基因检测表明，包含三个OPRD1启动子CpG的DNA片段能够调节基因表达。总之，我们的结果表明OPRD1启动子高甲基化与AD风险相关。
