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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Polymorphisms in the angiotensin-converting enzyme gene are associated wit unipolar depression, ACE activity and hypercortisolism.
Mol. Psychiatry 11, 1003-1015 (2006)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
major depression; susceptibility; SNP rs4291; ACE; cortisol
ISSN (print) / ISBN
1359-4184
e-ISSN
1476-5578
Zeitschrift
Molecular Psychiatry
Quellenangaben
Band: 11,
Heft: 11,
Seiten: 1003-1015
Verlag
Nature Publishing Group
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)