DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression.
BACKGROUND
The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ~40%-50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood.


METHODS
The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls.


RESULTS
We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04).


CONCLUSIONS
The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders.
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany. Peter.Zill@med.uni-muenchen.de
Peter
P
Zill
Thomas C
TC
Baghai
Cornelius
C
Schüle
Christoph
C
Born
Clemens
C
Früstück
Andreas
A
Büttner
Wolfgang
W
Eisenmenger
Gabriella
G
Varallo-Bedarida
Rainer
R
Rupprecht
Hans-Jürgen
HJ
Möller
Brigitta
B
Bondy
D000328:Adult; D000368:Aged; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology / Q000235:genetics; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D003865:Major Depressive Disorder / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011180:Postmortem Changes; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult
D015415:Biomarkers; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A