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Baghai, T.C.* ; Binder, E.B.* ; Schule, C.* ; Salyakina, D.* ; Eser, D.* ; Lucae, S.* ; Zwanzger, P.* ; Haberger, C.* ; Zill, P.* ; Ising, M.* ; Deiml, T.* ; Uhr, M.* ; Illig, T. ; Wichmann, H.-E. ; Modell, S.* ; Nothdurfter, C.* ; Holsboer, F.* ; Müller-Myhsok, B.* ; Möller, H.J.* ; Rupprecht, R.* ; Bondy, B.*

Polymorphisms in the angiotensin-converting enzyme gene are associated wit unipolar depression, ACE activity and hypercortisolism.

Mol. Psychiatry 11, 1003-1015 (2006)
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Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between 35 single-nucleotide polymorphisms (SNPs) and an insertion/deletion (I/D)-polymorphism in the ACE gene and the susceptibility for unipolar major depression together with the genetic association with ACE serum activity and functional parameters of the HPA system. Two independent case/control samples with a total of 843 unrelated unipolar depressed patients and 1479 healthy controls were investigated. A case/control sample was screened to detect genetic associations with unipolar major depression. In addition, a replication sample was used to confirm the detected associations and to further investigate functional consequences of the genetic variants associated with depression. In the screening sample, two SNPs within the ACE gene were significantly associated with unipolar major depression. The association with unipolar major depression of one SNP (rs4291) located in the promoter region of the ACE gene was confirmed in our replication sample. The T-allele of this SNP was associated with depression and depressed T-allele carriers showed higher ACE serum activity and HPA-axis hyperactivity. Variants of the ACE gene such as SNP rs4291 are suggested susceptibility factors for unipolar major depression. We could show that SNP rs4291 influences ACE activity and HPA-axis hyperactivity and might therefore represent a common pathophysiologic link for unipolar depression and cardiovascular disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords major depression; susceptibility; SNP rs4291; ACE; cortisol
Language english
Publication Year 2006
HGF-reported in Year 0
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Journal Molecular Psychiatry
Quellenangaben Volume: 11, Issue: 11, Pages: 1003-1015 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
POF-Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-503900-003
DOI 10.1038/sj.mp.4001884
Scopus ID 33750352319
Erfassungsdatum 2006-11-09
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