Liu Linlin, Yang Xiaopei, Zhao Fei, Gao Changqing, Zhang Ning, Bao Jianjun, Li Kuan, Zhang Xulan, Lu Xiaoxiao, Ruan Ye, Zhong Shurong
School of Forensic Medicine, Kunming Medical University, Kunming, China.
Forensic biology identification laboratory, Judicial Identification Center of Kunming Medical University, Kunming, China.
Am J Drug Alcohol Abuse. 2021 Nov 2;47(6):694-703. doi: 10.1080/00952990.2021.1973486. Epub 2021 Sep 28.
Alcohol use disorder (AUD) is one of the most serious public health problems worldwide. The and 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 and has been performed in Chinese Han patients with AUD.
To investigate whether methylation patterns of and are associated with susceptibility to AUD in Chinese Han males.
DNA methylation of the and 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 < .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 , in which 3 CpG sites showed significant hypermethylation ( < .01). Age had no significant effect on the DNA methylation levels of these two genes.
Our study demonstrates that DNA hypermethylation of the and promoter regions is associated with an increased risk of AUD, which may help to explain the pathogenesis and progression of AUD.
酒精使用障碍（AUD）是全球最严重的公共卫生问题之一。OPRM1和ALDH2基因是奖赏和酒精代谢途径中的重要因素，其DNA甲基化模式与AUD密切相关且具有人群特异性。中国汉族是世界上人口最多的民族，该群体中AUD情况严重。尚未对中国汉族AUD患者进行关于OPRM1和ALDH2的表观遗传学研究。
探讨OPRM1和ALDH2的甲基化模式是否与中国汉族男性AUD易感性相关。
采用亚硫酸氢盐焦磷酸测序法研究云南省患AUD的中国汉族男性（50名对照，90名AUD患者）中OPRM1和ALDH2启动子的DNA甲基化情况。
在AUD组中，与对照组相比，OPRM1发生高甲基化（p <.01），但ALDH2甲基化水平无显著差异（p >.05）。OPRM1的9个CpG位点（p <.05）和ALDH2的2个CpG位点（p >.01）发生高甲基化。吸烟促进AUD介导的OPRM1高甲基化，其中3个CpG位点显示出显著的高甲基化（p <.01）。年龄对这两个基因的DNA甲基化水平无显著影响。
我们的研究表明，OPRM1和ALDH2启动子区域的DNA高甲基化与AUD风险增加相关，这可能有助于解释AUD的发病机制和进展。
