title: Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age.
abstract: 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.
authors.affiliation: Departments of Genetic Epidemiology in Psychiatry Addictive Behavior and Addiction Medicine Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany, Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Germany Institute of Neuroscience and Medicine, Research Centre Jülich, Germany Department of Genomics, Life & Brain Center Institute of Human Genetics University of Bonn, Germany and German Center for Neurodegenerative Disorders (DZNE), Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
authors.forename: Martin
authors.initials: M
authors.lastname: Grosshans
authors.forename: Josef
authors.initials: J
authors.lastname: Frank
authors.forename: Jana
authors.initials: J
authors.lastname: Strohmaier
authors.forename: Christoph
authors.initials: C
authors.lastname: von der Goltz
authors.forename: Osman
authors.initials: O
authors.lastname: El-Maarri
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
mesh_terms: D000328:Adult; D000367:Age Factors; D000437:Alcoholism / Q000235:genetics* / Q000534:rehabilitation; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D059647:Gene-Environment Interaction; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D012737:Sex Factors; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins