Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

  • Authors:
    • Huihui Ji
    • Xuting Xu
    • Guili Liu
    • Huifen Liu
    • Qinwen Wang
    • Wenwen Shen
    • Longhui Li
    • Xiaohu Xie
    • Haochang Hu
    • Lei Xu
    • Wenhua Zhou
    • Shiwei Duan
  • View Affiliations

  • Published online on: December 12, 2017     https://doi.org/10.3892/etm.2017.5615
  • Pages:2128-2133
Metrics: HTML 0 views | PDF 0 views     Cited By: 0 citations

Abstract

Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (P<0.05). Male METH addicts exhibited significantly higher DRD4 CpG1, CpG2 and CpG4 methylation levels compared with sex‑matched controls (P<0.05). In heroin addicts, a positive correlation was observed between depression‑dejection and DRD4 CpG5 methylation (r=0.537, P=0.039) whereas there was a negative correlation between drug usage frequency and CpG1 methylation (r=‑0.632, P=0.011). In METH addicts, methylation levels were not significantly associated with depression‑dejection and drug usage frequency. In addition, luciferase assays demonstrated that the target sequence of the DRD4 promoter upregulates gene expression. The results of the present study suggest that DNA methylation of DRD4 may be responsible for the pathophysiology of drug addiction.

Related Articles

Journal Cover

February 2018
Volume 15 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Ji, H., Xu, X., Liu, G., Liu, H., Wang, Q., Shen, W. ... Duan, S. (2018). Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction. Experimental and Therapeutic Medicine, 15, 2128-2133. https://doi.org/10.3892/etm.2017.5615
MLA
Ji, H., Xu, X., Liu, G., Liu, H., Wang, Q., Shen, W., Li, L., Xie, X., Hu, H., Xu, L., Zhou, W., Duan, S."Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction". Experimental and Therapeutic Medicine 15.2 (2018): 2128-2133.
Chicago
Ji, H., Xu, X., Liu, G., Liu, H., Wang, Q., Shen, W., Li, L., Xie, X., Hu, H., Xu, L., Zhou, W., Duan, S."Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction". Experimental and Therapeutic Medicine 15, no. 2 (2018): 2128-2133. https://doi.org/10.3892/etm.2017.5615