4.6 Article

Elevated OPRD1 promoter methylation in Alzheimer's disease patients

Journal

PLOS ONE
Volume 12, Issue 3, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0172335

Keywords

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Funding

  1. National Natural Science Foundation of China [81471398, 81070873, 81371469]
  2. 973 program from Ministry of Science and Technology of China [2013CB835100]
  3. National Natural Science Foundation of Zhejiang [LY15090010]
  4. Public technology research and social development project of Zhejiang Province [2015C33155]
  5. Natural Science Foundation of Zhejiang Province [Y15H090032]
  6. Ningbo Natural Science Fund [2014A610257]
  7. Graduate Outstanding Dissertation Fund of Ningbo University [014-F01660148000]
  8. Disciplinary Project of Ningbo University [1301350104900]
  9. K. C. Wong Magna Fund in Ningbo University

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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 hyper-methylation is associated with the risk of AD.

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