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.

译文

:作为老年痴呆症的痴呆前期,轻度认知障碍(MCI)涉及认知障碍的发生和发展。阿片受体在调节学习和认知中起关键作用。我们的研究集中在新疆维吾尔族和汉族人群中OPRK1和OPRM1甲基化与MCI的关系。使用亚硫酸氢焦磷酸测序法测量DNA甲基化。我们的结果表明,OPRK1在新疆汉族MCI女性中明显超甲基化。同时,新疆维吾尔族和汉族人群中OPRM1 CpG1高甲基化和CpG2-4低甲基化分别与MCI风险相关。我们的研究表明,新疆(中国西北部)的OPRK1和OPRM1甲基化程度明显高于浙江(中国东南部)汉族健康对照。我们的结果表明,OPRK1启动子甲基化与性别,种族,衰老和环境变化有关,而OPRM1启动子甲基化与血脂和生活区有关。双荧光素酶报告基因检测表明,OPRK1和OPRM1的启动子片段能够上调基因表达。总之,我们的发现为新疆维吾尔族和汉族人群的OPRK1和OPRM1甲基化提供了新颖的方面。

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