Elevated OPRD1 promoter methylation in Alzheimer's disease patients

Huihui Ji; Yunliang Wang; Guili Liu; Lan Chang; Zhongming Chen; Dongsheng Zhou; Xuting Xu; Wei Cui; Qingxiao Hong; Liting Jiang; Jinfeng Li; Xiaohui Zhou; Ying Li; Zhiping Guo; Qin Zha; Yanfang Niu; Qiuyan Weng; Shiwei Duan; Qinwen Wang

doi:10.1371/journal.pone.0172335

Elevated OPRD1 promoter methylation in Alzheimer's disease patients

PLoS One. 2017 Mar 2;12(3):e0172335. doi: 10.1371/journal.pone.0172335. eCollection 2017.

Authors

Huihui Ji¹, Yunliang Wang², Guili Liu¹, Lan Chang¹, Zhongming Chen³, Dongsheng Zhou³, Xuting Xu¹, Wei Cui¹, Qingxiao Hong¹, Liting Jiang¹, Jinfeng Li², Xiaohui Zhou⁴, Ying Li⁵, Zhiping Guo⁶, Qin Zha⁷, Yanfang Niu⁷, Qiuyan Weng⁷, Shiwei Duan¹, Qinwen Wang¹

Affiliations

¹ Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
² Department of Neurology, the 148 Central Hospital of PLA, Zibo, Shandong, China.
³ Ningbo Kangning Hospital, Ningbo, Zhejiang, China.
⁴ Department of Internal Medicine for Cadres, the First Affiliated Hospital of Xinjiang Medical University, Urumchi, China.
⁵ Ningbo No. 1 Hospital, Ningbo, Zhejiang, China.
⁶ School of Medicine, Lishui University, Lishui, Zhejiang, China.
⁷ The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.

Abstract

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.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / genetics*
Base Sequence
Case-Control Studies
DNA Methylation*
Female
HEK293 Cells
Humans
Male
Middle Aged
Promoter Regions, Genetic / genetics*
Receptors, Opioid, delta / genetics*

Substances

OPRD1 protein, human
Receptors, Opioid, delta

Grants and funding

This research was supported by grants from the National Natural Science Foundation of China (81471398, 81070873, and 81371469), the 973 program from the Ministry of Science and Technology of China (2013CB835100), National Natural Science Foundation of Zhejiang (LY15090010), Public technology research and social development project of Zhejiang Province (2015C33155), Natural Science Foundation of Zhejiang Province (Y15H090032), Ningbo Natural Science Fund (2014A610257), Graduate Outstanding Dissertation Fund of Ningbo University (014-F01660148000), the Disciplinary Project of Ningbo University (B01350104900), and the K. C. Wong Magna Fund in Ningbo University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.