A significant association between BDNF promoter methylation and the risk of drug addiction

Gene. 2016 Jun 10;584(1):54-59. doi: 10.1016/j.gene.2016.03.010. Epub 2016 Mar 11.

Abstract

As a member of the neurotrophic factor family, brain derived neurotrophic factor (BDNF) plays an important role in the survival and differentiation of neurons. The aim of our work was to evaluate the role of BDNF promoter methylation in drug addiction. A total of 60 drug abusers (30 heroin and 30 methylamphetamine addicts) and 52 healthy age- and gender-matched controls were recruited for the current case control study. Bisulfite pyrosequencing technology was used to determine the methylation levels of five CpGs (CpG1-5) on the BDNF promoter. Among the five CpGs, CpG5 methylation was significantly lower in drug abusers than controls. Moreover, significant associations were found between CpG5 methylation and addictive phenotypes including tension-anxiety, anger-hostility, fatigue-inertia, and depression-dejection. In addition, luciferase assay showed that the DNA fragment of BDNF promoter played a key role in the regulation of gene expression. Our results suggest that BDNF promoter methylation is associated with drug addiction, although further studies are needed to understand the mechanisms by which BDNF promoter methylation contributes to the pathophysiology of drug addiction.

Keywords: Addiction; BDNF; Heroin; Methylamphetamine; Methylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amphetamine-Related Disorders / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cell Line
  • DNA Methylation*
  • Female
  • Genetic Predisposition to Disease*
  • HEK293 Cells
  • Heroin Dependence / genetics*
  • Humans
  • Male
  • Methamphetamine / adverse effects
  • Promoter Regions, Genetic*

Substances

  • Brain-Derived Neurotrophic Factor
  • Methamphetamine