title: Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving.
abstract: Dopaminergic neurotransmission plays a crucial role in the genesis and maintenance of alcohol dependence. Epigenetic regulation via promoter specific DNA methylation of the dopamine transporter gene (DAT) may influence altered dopaminergic neurotransmission in alcoholism. Aim of the present study was to investigate DNA promoter methylation of DAT in early alcohol withdrawal and in relation to alcohol craving. We analyzed blood samples of 76 patients admitted for detoxification treatment and compared them to 35 healthy controls. Methylation specific quantitative real-time PCR was used to measure the promoter specific DNA methylation of the dopamine transporter. We assessed the extent of alcohol craving using the obsessive compulsive drinking scale (OCDS). Compared to healthy controls we found a significant hypermethylation of the DAT-promoter (Mann-Whitney U-test: p=0.001). Ln-transformed methylation of the DAT-promoter was negatively associated with the OCDS (linear regression: Beta=-0.275, p=0.016), particularly with the obsessive subscale (Beta=-0.300, p=0.008). Findings of the present study show that the epigenetic regulation of the DAT-promoter is altered in patients undergoing alcohol withdrawal. Furthermore, hypermethylation of the DAT-promoter may play an important role in dopaminergic neurotransmission and is associated with decreased alcohol craving.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany. thomas.hillemacher@uk-erlangen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartl
authors.forename: Julia
authors.initials: J
authors.lastname: Wilhelm
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D003192:Compulsive Behavior / Q000235:genetics / Q000523:psychology; D019175:DNA Methylation / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009770:Obsessive Behavior / Q000235:genetics / Q000523:psychology; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000235:genetics* / Q000523:psychology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins