Journal of Neural Transmission

, Volume 117, Issue 4, pp 513–519

DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence

  • Marc Andre Nicolas Muschler
  • Thomas Hillemacher
  • Cornelia Kraus
  • Johannes Kornhuber
  • Stefan Bleich
  • Helge Frieling
Biological Psychiatry - Original Article

DOI: 10.1007/s00702-010-0378-7

Cite this article as:
Muschler, M.A.N., Hillemacher, T., Kraus, C. et al. J Neural Transm (2010) 117: 513. doi:10.1007/s00702-010-0378-7

Abstract

Hypothalamic–pituitary–adrenal (HPA) axis dysfunction has been implicated in the pathogenesis of addictive behaviour and especially in alcohol craving. The pro-opiomelanocortin gene (POMC), encoding a 241 amino acids stretching polypeptide hormone precursor, plays an important role in the regulation of the HPA, and is prone to epigenetic regulation due to promoter-related DNA methylation. Aim of the present study therefore was to investigate possible differences in promoter-related DNA methylation in patients suffering from alcohol dependence compared to healthy controls. We analysed the DNA methylation of the 5′ promoter of the POMC gene that is embedded in a CpG island using bisulfite sequencing in 145 alcohol-dependent patients and 37 healthy controls taken from the Franconian Alcoholism Research Studies. We found only marginal, hence significant differences at single CpG sites between patients and controls. We identified a cluster of CpGs showing a significant association with alcohol craving in the patients group. These results implicate that epigenetic changes possibly due to alcohol intake may contribute to craving via promoting HPA-axis dysfunction. Further studies should more closely investigate the impact of these changes on the several derivatives of the POMC gene.

Keywords

AlcoholCravingDNA methylationPOMCHPA axis

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Marc Andre Nicolas Muschler
    • 1
    • 2
  • Thomas Hillemacher
    • 1
    • 2
  • Cornelia Kraus
    • 3
  • Johannes Kornhuber
    • 2
  • Stefan Bleich
    • 1
    • 2
  • Helge Frieling
    • 1
    • 2
  1. 1.Department of Psychiatry, Socialpsychiatry and Psychotherapy, Center for Addiction ResearchHannover Medical SchoolHannoverGermany
  2. 2.Department of Psychiatry and PsychotherapyUniversity Hospital of ErlangenErlangenGermany
  3. 3.Institute of Human GeneticsFriedrich-Alexander University Erlangen-NurembergErlangenGermany