Hypermethylation of the OPRM1 and ALDH2 promoter regions in Chinese Han males with alcohol use disorder in Yunnan Province

ABSTRACT

Background

Alcohol use disorder (AUD) is one of the most serious public health problems worldwide. The OPRM1 and ALDH2 genes are important factors in the reward and alcohol metabolism pathways, and their DNA methylation patterns are closely related to AUD and are population-specific. Chinese Han people are the most populous ethnic group in the world, and this group experiences severe AUD. No epigenetic study on OPRM1 and ALDH2 has been performed in Chinese Han patients with AUD.

Objectives

To investigate whether methylation patterns of OPRM1 and ALDH2 are associated with susceptibility to AUD in Chinese Han males.

Methods

DNA methylation of the OPRM1 and ALDH2 promoters was studied in Chinese Han males with AUD in Yunnan Province (N = 50 controls, N = 90 individuals with AUD) using the bisulfite pyrosequencing method.

Results

In the AUD group, compared with the control group, OPRM1 was hypermethylated(p < .01) but there was no significant difference in the methylation level of ALDH2 (p > .05). 9 CpG sites of OPRM1 (p < .05) and 2 CpG sites of ALDH2 (p > .01) were hypermethylated. Smoking promoted AUD-mediated hypermethylation of OPRM1, in which 3 CpG sites showed significant hypermethylation (p < .01). Age had no significant effect on the DNA methylation levels of these two genes.

Conclusions

Our study demonstrates that DNA hypermethylation of the OPRM1 and ALDH2 promoter regions is associated with an increased risk of AUD, which may help to explain the pathogenesis and progression of AUD.

KEYWORDS:

• Alcohol use disorder
• OPRM1
• ALDH2
• DNA methylation
• Chinese Han males

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the National Natural ScienceFoundation of China [grant numbers 81660232, 81000577]; the  100 Outstanding Young Scientists and Technicions Program from Kunming Medical University [grant numbers 60117190413, 60117190447]; the Joint Fund from the Yunnan Provincial Science and Technology Department & Kunming Medical University [grant number 2015FB011]; the Major Project of Biomedicine from Yunnan Provincial Science and Technology Department [grant number2019ZF003].