Ji Huihui, Liu Guili, Xu Xuting, Liu Huifen, Xu Lei, Hu Haochang, Chen Yingmin, Hong Qinxiao, Wang Qinwen, Shen Wenwen, Li Longhui, Xie Xiaohu, Zhou Wenhua, Duan Shiwei
Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, Ningbo, Zhejiang 315010, P.R. China.
Exp Ther Med. 2018 Sep;16(3):2392-2398. doi: 10.3892/etm.2018.6514. Epub 2018 Jul 24.
Heroin and methamphetamine (METH) addiction continues to be a major social, economic and therapeutic problem worldwide. The opioid pathway may mediate the effects of addictive drugs. However, the potential correlation between the κ1 opioid receptor (OPRK1) and drug addiction has not yet been characterized. The aim of the present study was to investigate the potential association between methylation of the OPRK1 promoter and substance abuse. Bisulfite pyrosequencing technology was used to determine the levels of OPRK1 promoter methylation in 60 drug abusers (30 heroin and 30 METH addicts) and 52 controls, observed to exhibit no significant differences in age or gender. The results indicated that levels of OPRK1 promoter methylation were significantly higher in drug addicts when compared with controls (P=2.43×10). Significant correlations between OPRK1 promoter methylation and the length and frequency of drug use were also observed in male heroin addicts (length: r=0.661, P=0.007; frequency: r=-0.684, P=0.005). In addition, a luciferase reporter gene assay indicated that the OPRK1 promoter fragment was able to regulate gene expression (fold change between two groups >32.12, P≤0.0001). In conclusion, results of the present study indicate that methylation of the OPRK1 promoter contributes to the pathophysiology of drug addiction.
海洛因和甲基苯丙胺（冰毒）成瘾仍是全球范围内一个重大的社会、经济和治疗问题。阿片类物质途径可能介导成瘾药物的作用。然而，κ1阿片受体（OPRK1）与药物成瘾之间的潜在关联尚未得到明确阐述。本研究的目的是调查OPRK1启动子甲基化与药物滥用之间的潜在关联。采用亚硫酸氢盐焦磷酸测序技术测定60名药物滥用者（30名海洛因成瘾者和30名冰毒成瘾者）及52名对照者的OPRK1启动子甲基化水平，这些对照者在年龄和性别上无显著差异。结果表明，与对照组相比，药物成瘾者的OPRK1启动子甲基化水平显著更高（P = 2.43×10）。在男性海洛因成瘾者中还观察到OPRK1启动子甲基化与吸毒时长和频率之间存在显著相关性（时长：r = 0.661，P = 0.007；频率：r = -0.684，P = 0.005）。此外，荧光素酶报告基因检测表明，OPRK1启动子片段能够调节基因表达（两组间倍数变化>32.12，P≤0.0001）。总之，本研究结果表明，OPRK1启动子甲基化参与了药物成瘾的病理生理过程。
