title: OPRK1 promoter hypermethylation increases the risk of Alzheimer's disease.
abstract: As a member of the opioid family, κ-opioid receptors play important role in cognitive and learning functions. The purpose of this study was to evaluate the association of OPRK1 promoter methylation with Alzheimer's disease (AD). OPRK1 DNA methylation levels of 48 cases and 58 well matched controls were measured using the bisulphite pyrosequencing technology. Our results showed that there was a significant correlation between three CpG sites on the OPRK1 promoter region (r>=0.715, p<0.001). Thus, the mean methylation value of the three CpG sites was used for the case-control comparison. And our results showed there was a significantly higher OPRK1 promoter methylation in AD cases than in controls (p=0.006, adjusted p=0.012). Subsequent luciferase reporter assay showed the CpGs containing fragment of OPRK1 promoter significantly increased the expression of reporter gene (Fold=2.248, p=0.0235). In summary, our results suggested that OPRK1 promoter hypermethylation might increase the risk of AD through its regulation on the gene expression of OPRK1.
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Huihui
authors: H
authors: Ji
authors: Department of Neurology, the 148 Central Hospital of PLA, Zibo, Shandong 255000, China. Electronic address: wangyunliang81@163.com.
authors: Yunliang
authors: Y
authors: Wang
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Guili
authors: G
authors: Liu
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Xuting
authors: X
authors: Xu
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Dongjun
authors: D
authors: Dai
authors: Ningbo Kangning Hospital, Zhejiang 315200, China.
authors: Zhongming
authors: Z
authors: Chen
authors: Ningbo Kangning Hospital, Zhejiang 315200, China.
authors: Dongsheng
authors: D
authors: Zhou
authors: Department of Internal Medicine for Cadres, the First Affiliated Hospital of Xinjiang Medical University, Urumchi 830000, China.
authors: Xiaohui
authors: X
authors: Zhou
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Liyuan
authors: L
authors: Han
authors: Ningbo No. 1 Hospital, Zhejiang 315200, China.
authors: Ying
authors: Y
authors: Li
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Renjie
authors: R
authors: Zhuo
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Qingxiao
authors: Q
authors: Hong
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Liting
authors: L
authors: Jiang
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Xiaonan
authors: X
authors: Zhang
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Yu
authors: Y
authors: Liu
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Lei
authors: L
authors: Xu
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Lan
authors: L
authors: Chang
authors: Department of Neurology, the 148 Central Hospital of PLA, Zibo, Shandong 255000, China.
authors: Jinfeng
authors: J
authors: Li
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors: Pengyuan
authors: P
authors: An
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: duanshiwei@nbu.edu.cn.
authors: Shiwei
authors: S
authors: Duan
authors: Ningbo Key Lab of Behavior Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: wangqinwen@nbu.edu.cn.
authors: Qinwen
authors: Q
authors: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D017473:Receptors, Opioid, kappa / Q000235:genetics* / Q000378:metabolism
chemical_list: C515653:OPRK1 protein, human; D017473:Receptors, Opioid, kappa
keywords: Alzheimer disease; DNA methylation; Expression; OPRK1; Promoter