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Comparing DRD2 Promoter Methylation Between Blood and Brain in Alcohol Dependence.

Wiebke Arfmann1, Johannes Achenbach1,2, Fiona Meyer-Bockenkamp1

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Alcohol and Alcoholism (Oxford, Oxfordshire)
|February 7, 2023
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Summary

Epigenetic regulation of the dopamine receptor D2 (DRD2) gene in alcohol use disorder (AUD) differs between brain and blood. Brain DRD2 promoter methylation changes in AUD, but blood samples do not reflect these brain alterations.

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Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • The dopamine receptor D2 (DRD2) gene plays a crucial role in addiction, with both genetic and epigenetic factors influencing its regulation.
  • Previous studies indicate altered DRD2 methylation in alcohol use disorder (AUD), with blood often used as a proxy for epigenetic changes.
  • However, direct comparisons of DRD2 methylation between blood and brain tissue in AUD are limited.

Purpose of the Study:

  • To investigate the relationship between DRD2 promoter methylation in post-mortem brain tissue and blood samples from individuals with and without AUD.
  • To determine if blood methylation patterns can accurately reflect DRD2 promoter methylation in specific brain regions affected by AUD.

Main Methods:

  • Analysis of post-mortem brain tissue (nucleus accumbens and hippocampus) and blood samples from 17 deceased AUD patients and 31 deceased controls.
  • Quantitative assessment of DNA methylation at CpG sites within the DRD2 promoter region.

Main Results:

  • Significant differences in DRD2 promoter methylation were observed in the nucleus accumbens and hippocampus of AUD individuals compared to controls.
  • Hypomethylated CpG sites targeting transcription factors involved in gene activation were identified in AUD brain samples.
  • Methylation patterns in blood did not significantly correlate with the observed DRD2 promoter methylation changes in the brain.

Conclusions:

  • Altered DRD2 gene transcription, potentially affecting reward pathways, is supported in AUD brain tissue.
  • While some brain regions may show comparable methylation to blood, blood DRD2 promoter methylation is not a reliable indicator of brain methylation status in AUD.