Rationale: Previous findings of the Franconian Alcoholism Research Studies showed that both the CAGn of the androgen receptor (AR) and the promoter methylation of the hypothalamic peptide proopiomelanocortin (POMC) were associated with craving of male alcohol-dependent patients.
Objectives: Based on the strong interactions between the hypothalamic-pituitary-gonadal (HPG) and the hypothalamic-pituitary-adrenal axis (HPA), this study investigated the relationships between the CAGn repeat of the AR, POMC promoter methylation and craving of male alcohol-dependent patients.
Methods: This analysis covers 84 male patients with a diagnosis of alcohol dependence (DSM-IV). We sequenced the POMC gene promoter using bisulfite modified DNA to display the methylation status. Furthermore, we sequenced the CAGn repeat within exon 1 of the AR gene. Craving was quantified by the Obsessive Compulsive Drinking Scale.
Results: We found an inverse correlation between the number of CAGn repeats of the AR and the POMC methylation status in this study. Altogether, the POMC promoter methylation accounted for 33 % of the relationship between CAGn AR polymorphism and craving.
Conclusions: This work shows that the AR and the POMC gene might functionally interact with each other and subsequently mediate craving in alcohol-dependent patients. The paper discusses different mechanisms which might underlie our findings involving sex hormones' and sex determining region of Y-gene's regulatory function on DNA-methyltransferase activity. In conclusion, the results give insight in the interaction between HPG and HPA axis. This study is a further step on the way to a better understanding of genetic and non-genetic factors underlying craving for alcohol.