Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age

Nieratschker, Vanessa and Grosshans, Martin and Frank, Josef and Strohmaier, Jana and von der Goltz, Christoph and El-Maarri, Osman and Witt, Stephanie H. and Cichon, Sven and Nöthen, Markus M. and Kiefer, Falk and Rietschel, Marcella. (2014) Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age. Addiction Biology, 19 (2). pp. 305-311.

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Chronic alcohol abuse and dependence are associated with dysfunctional dopaminergic neurotransmission in mesocorticolimbic circuits. Genetic and environmental factors have been shown to modulate susceptibility to alcohol dependence, and both may act through epigenetic mechanisms that can modulate gene expression, e.g. DNA methylation at CpG sites. Recent studies have suggested that DNA methylation patterns may change over time. However, few data are available concerning the rate of these changes in specific genes. A recent study found that hypermethylation of the promoter of the dopamine transporter (DAT) gene was positively correlated with alcohol dependence and negatively correlated with alcohol craving. The aim of the present study was to replicate these findings in a larger sample of alcohol-dependent patients and population-based controls matched for age and sex. No difference in methylation level was observed between patients and controls, and no difference in methylation level was observed before and after alcohol withdrawal in patients. However, patients with more severe craving showed a trend towards lower DAT methylation levels (P = 0.07), which is consistent with previous findings. Furthermore, in our overall sample, DAT methylation levels increased with age. Interestingly, a separate analysis of patients suggested that this finding was mainly driven by the patient group. Although the present data do not clarify whether chronic alcohol abuse is responsible for this phenomenon or merely enhances an ageing-specific process, our findings suggest that hypermethylation in alcohol-dependent patients is a consequence, rather than a cause, of the disorder.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Dec 2020 16:48
Deposited On:09 Dec 2020 16:48

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