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

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• 作者：Marc Andre Nicolas Muschler ; Thomas Hillemacher ; Cornelia Kraus ; Johannes Kornhuber ; Stefan Bleich and Helge Frieling
• 关键词：Alcohol ; Craving ; DNA methylation ; POMC ; HPA axis
• 刊名：Journal of Neural Transmission
• 出版年：2010
• 出版时间：April, 2010
• 年：2010
• 卷：117
• 期：4
• 页码：513-519
• 全文大小：277.8 KB

文摘

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.