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

Alcohol use disorder (AUD) is one of the most serious public health problems worldwide. The <i>OPRM1</i> and <i>ALDH2</i> 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 <i>OPRM1</i> and <i>ALDH2</i> has been performed in Chinese Han patients with AUD. To investigate whether methylation patterns of <i>OPRM1</i> and <i>ALDH2</i> are associated with susceptibility to AUD in Chinese Han males. DNA methylation of the <i>OPRM1</i> and <i>ALDH2</i> 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.
In the AUD group, compared with the control group, OPRM1 was hypermethylated(p &lt; .01) but there was no significant difference in the methylation level of ALDH2 (p &gt; .05). 9 CpG sites of OPRM1 (p &lt; .05) and 2 CpG sites of ALDH2 (p &gt; .01) were hypermethylated. Smoking promoted AUD-mediated hypermethylation of <i>OPRM1</i>, in which 3 CpG sites showed significant hypermethylation (<i>p</i> &lt; .01). Age had no significant effect on the DNA methylation levels of these two genes.
Our study demonstrates that DNA hypermethylation of the <i>OPRM1</i> and <i>ALDH2</i> promoter regions is associated with an increased risk of AUD, which may help to explain the pathogenesis and progression of AUD.