Epigenetic dysregulation of dopaminergic genes in eating disorders.
OBJECTIVE
The pathophysiology of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN) has been linked to an impaired dopaminergic neurotransmission, still the origin of this disturbance remains unknown. The aim of the present study was, therefore, to evaluate whether the expression of dopaminergic genes is altered in the blood of patients suffering from eating disorders and if these alterations can be explained by changes in the promoter specific DNA methylation of the genes.


METHODS
We used quantitative real-time PCR to measure both the expression and the promoter specific DNA methylation of the dopamine transporter (DAT), and the D2 (DRD2) and D4 receptor (DRD4) gene in the blood of 46 patients (22 AN, 24 BN) and 30 healthy controls.


RESULTS
Patients showed an elevated expression of DAT mRNA when compared with the controls and a downregulation of the DRD₂ expression. The upregulation of the DAT gene was accompanied by a hypermethylation of the gene's promoter in the AN and BN group while a significant hypermethylation of the DRD₂ promoter was only present in the AN group. No differences in expression or methylation were found for the other dopamine receptors investigated.


CONCLUSIONS
Our study shows a disturbed expression of dopaminergic genes that is accompanied by a dysregulation of the epigenetic DNA methylation. Further studies are necessary to provide more insight into the epigenetic dysregulation of the dopaminergic neurotransmission in the pathophysiology of eating disorders.
Frieling
Helge
H
Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Erlangen, Germany. helge.frieling@uk-erlangen.de
Römer
Konstanze D
KD
Scholz
Sarah
S
Mittelbach
Franziska
F
Wilhelm
Julia
J
De Zwaan
Martina
M
Jacoby
Georg E
GE
Kornhuber
Johannes
J
Hillemacher
Thomas
T
Bleich
Stefan
S
D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics; D004298:Dopamine / Q000097:blood / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000097:blood / Q000235:genetics*; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000235:genetics*; D001068:Feeding and Eating Disorders / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000097:blood / Q000235:genetics*; D015854:Up-Regulation
D050483:Dopamine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D004298:Dopamine