Elevated methylation of OPRM1 and OPRL1 genes in Alzheimer's disease

Xu,Chunshuang; Liu,Guili; Ji,Huihui; Chen,Weihua; Dai,Dongjun; Chen,Zhongming; Zhou,Dongsheng; Xu,Lei; Hu,Haochang; Cui,Wei; Chang,Lan; Zha,Qin; Li,Liping; Duan,Shiwei; Wang,Qinwen

doi:10.3892/mmr.2018.9424

Elevated methylation of OPRM1 and OPRL1 genes in Alzheimer's disease

Authors:
- Chunshuang Xu
- Guili Liu
- Huihui Ji
- Weihua Chen
- Dongjun Dai
- Zhongming Chen
- Dongsheng Zhou
- Lei Xu
- Haochang Hu
- Wei Cui
- Lan Chang
- Qin Zha
- Liping Li
- Shiwei Duan
- Qinwen Wang
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Affiliations: Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Department of Science and Education, Ningbo No. 9 Hospital, Ningbo, Zhejiang 315010, P.R. China, Geriatrics Department, Ningbo Kangning Hospital, Ningbo, Zhejiang 315200, P.R. China, Department of Science and Education, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315200, P.R. China
Published online on: August 24, 2018 https://doi.org/10.3892/mmr.2018.9424
Pages: 4297-4302
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have suggested that increased opioid receptor κ1 (OPRK1) and opioid receptor δ1 (OPRD1) methylation levels are involved in Alzheimer's disease (AD). In the present study, the methylation levels of two opioid receptor genes, opioid receptor µ1 (OPRM1) and opioid related nociceptin receptor 1 (OPRL1), were analyzed for their association with AD. Gene methylation levels were measured using bisulfite pyrosequencing in DNA samples derived from blood samples of 51 AD patients and 63 controls. The results indicated that there were significantly elevated promoter methylation levels of OPRM1 and OPRL1 in AD (OPRM1: P=0.007; OPRL1: P=2.987x10‑6). Dual‑luciferase reporter gene assays demonstrated that the promoter fragments of these two genes were able to promote gene expression (OPRM1: Fold‑change=2.616, P=0.003; OPRL1: Fold change=11.395, P=0.007). In addition, receiver operating characteristic analyses further indicated that a methylation panel of four opioid receptor genes (area under the curve=0.848, sensitivity=0.723, and specificity=0.879) performed well in the prediction of AD. These results suggested that opioid receptor genes may be used as potential methylation biomarkers for the diagnosis of AD.

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