title: Association of OPRK1 and OPRM1 methylation with mild cognitive impairment in Xinjiang Han and Uygur populations.
abstract: As the pre-dementia phase of Alzheimer disease, mild cognitive impairment (MCI) involves the onset and development of cognitive impairments. Opioid receptors play pivotal roles in the regulation of learning and cognition. Our study focused on the association of OPRK1 and OPRM1 methylation with MCI in Xinjiang Uygur and Han populations. DNA methylation was measured using bisulphite pyrosequencing method. Our results indicated OPRK1 was significantly hypermethylated in Xinjiang Han MCI females. Meanwhile, OPRM1 CpG1 hypermethylation and CpG2-4 hypomethylation were associated with MCI risk in Xinjiang Uygur and Han, respectively. Our study showed that OPRK1 and OPRM1 were significantly hypermethylated in Xinjiang (Northwest China) than Zhejiang (Southeast China) Han Chinese healthy controls. Our results showed that OPRK1 promoter methylation was related to gender, ethnicity, aging, and environmental changes, while OPRM1 promoter methylation was related to blood lipids and living regions. Dual-luciferase reporter gene assays revealed that promoter fragments of OPRK1 and OPRM1 were able to upregulate gene expression. In summary, our findings provided novel aspects of OPRK1 and OPRM1 methylation in Xinjiang Uygur and Han populations.
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Guili
authors.initials: G
authors.lastname: Liu
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Ji
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Chunshuang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chang
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Ye
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Haochang
authors.initials: H
authors.lastname: Hu
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine for Cadres, The First Affiliated Hospital of Xinjiang Medical University, Urumchi 830000, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: duanshiwei@nbu.edu.cn.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
authors.affiliation: Medical Genetics Center, School of Medicine at Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: wangqinwen@nbu.edu.cn.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D044466:Asian People; D002681:China; D060825:Cognitive Dysfunction / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: C515653:OPRK1 protein, human; C485764:OPRM1 protein, human; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
keywords: DNA methylation; Mild cognitive impairment; OPRK1; OPRM1; Opioid receptor; Peripheral blood