DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence.
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.
Muschler
Marc Andre Nicolas
MA
Department of Psychiatry, Center for Addiction Research, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. muschler.marc@mh-hannover.de
Hillemacher
Thomas
T
Kraus
Cornelia
C
Kornhuber
Johannes
J
Bleich
Stefan
S
Frieling
Helge
H
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
D006993:Hypnotics and Sedatives; D002719:Chlormethiazole; D011333:Pro-Opiomelanocortin