title: DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence.
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.
authors.affiliation: Department of Psychiatry, Center for Addiction Research, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. muschler.marc@mh-hannover.de
authors.forename: Marc Andre Nicolas
authors.initials: MA
authors.lastname: Muschler
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kraus
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D002719:Chlormethiazole / Q000627:therapeutic use; D018899:CpG Islands; D019175:DNA Methylation; D004327:Drinking Behavior; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D008297:Male; D008606:Mental Processes; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D002719:Chlormethiazole; D011333:Pro-Opiomelanocortin