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.
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.
Authors: Stefan Ehrlich; Deike Weiss; Roland Burghardt; Carmen Infante-Duarte; Simone Brockhaus; Marc A Muschler; Stefan Bleich; Ulrike Lehmkuhl; Helge Frieling Journal: J Psychiatr Res Date: 2010-02-21 Impact factor: 4.791
Authors: M Ansseau; J Besson; M Lejoyeux; E Pinto; U Landry; M Cornes; F Deckers; A Potgieter; J Ades Journal: Eur Addict Res Date: 2000-06 Impact factor: 3.015
Authors: B Lenz; H Frieling; C Jacob; A Heberlein; J Kornhuber; S Bleich; T Hillemacher Journal: Pharmacogenomics J Date: 2009-11-03 Impact factor: 3.550
Authors: M Brandeis; D Frank; I Keshet; Z Siegfried; M Mendelsohn; A Nemes; V Temper; A Razin; H Cedar Journal: Nature Date: 1994-09-29 Impact factor: 49.962
Authors: Kati Härkönen; Ilpo Huhtaniemi; Juha Mäkinen; Doris Hübler; Kerttu Irjala; Markku Koskenvuo; Michael Oettel; Olli Raitakari; Farid Saad; Pasi Pöllänen Journal: Int J Androl Date: 2003-06
Authors: Tillmann H C Kruger; Christopher Sinke; Jonas Kneer; Gilian Tenbergen; Abdul Qayyum Khan; Alexandra Burkert; Linda Müller-Engling; Harald Engler; Hannah Gerwinn; Nicole von Wurmb-Schwark; Alexander Pohl; Simone Weiß; Till Amelung; Sebastian Mohnke; Claudia Massau; Christian Kärgel; Martin Walter; Kolja Schiltz; Klaus M Beier; Jorge Ponseti; Boris Schiffer; Henrik Walter; Kirsten Jahn; Helge Frieling Journal: Transl Psychiatry Date: 2019-01-18 Impact factor: 6.222