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Glucocorticoid-related genetic susceptibility for Alzheimer's disease

de Quervain, Dominique J.-F. and Poirier, Raphael and Wollmer, M. Axel and Grimaldi, Luigi M. E. and Tsolaki, Magdalini and Streffer, Johannes R. and Hock, Christoph and Nitsch, Roger M. and Mohajeri, M. Hasan and Papassotiropoulos, Andreas. (2004) Glucocorticoid-related genetic susceptibility for Alzheimer's disease. Human Molecular Genetics, Vol. 13, H. 1. pp. 47-52.

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Official URL: http://edoc.unibas.ch/dok/A5257178

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Abstract

Because glucocorticoid excess increases neuronal vulnerability, genetic variations in the glucocorticoid system may be related to the risk for Alzheimer's disease (AD). We analyzed single-nucleotide polymorphisms in 10 glucocorticoid-related genes in a population of 814 AD patients and unrelated control subjects. Set-association analysis revealed that a rare haplotype in the 5' regulatory region of the gene encoding 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) was associated with a 6-fold increased risk for sporadic AD. Results of a reporter-gene assay indicated that the rare risk-associated haplotype altered HSD11B1 transcription. HSD11B1 controls tissue levels of biologically active glucocorticoids and thereby influences neuronal vulnerability. Our results indicate that a functional variation in the glucocorticoid system increases the risk for AD, which may have important implications for the diagnosis and treatment of this disease.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Kognitive Neurowissenschaften (de Quervain)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Kognitive Neurowissenschaften (de Quervain)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Cognitive Neuroscience (de Quervain)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas and de Quervain, Dominique J.-F.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0964-6906
e-ISSN:1460-2083
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Nov 2017 09:54
Deposited On:22 Mar 2012 13:32

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