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- Title
Glucocorticoid-related genetic susceptibility for Alzheimer's disease.
- Authors
de Quervain, Dominique J-F; Poirier, Raphael; Wollmer, M Axel; Grimaldi, Luigi M E; Tsolaki, Magdalini; Streffer, Johannes R; Hock, Christoph; Nitsch, Roger M; Mohajeri, M Hasan; Papassotiropoulos, Andreas
- 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.
- Publication
Human molecular genetics, 2004, Vol 13, Issue 1, p47
- ISSN
0964-6906
- Publication type
Journal Article
- DOI
10.1093/hmg/ddg361