Association of OPRK1 and OPRM1 methylation with mild cognitive impairment in Xinjiang Han and Uygur populations

- Association of OPRK1/OPRM1 methylation with MCI in Uygur and Han groups was focused.
- DNA methylation was measured using bisulphite pyrosequencing method.
- A female-specific hypermethylation of OPRK1 in Han MCI group was identified.
- OPRM1 methylation was differently associated with MCI in Xinjiang Uygur and Han.
- Promoter fragments of OPRK1 and OPRM1 were able to upregulate gene expression.

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.