Journal Article

Glucocorticoid-related genetic susceptibility for Alzheimer's disease

Dominique J.-F. de Quervain, Raphael Poirier, M. Axel Wollmer, Luigi M.E. Grimaldi, Magdalini Tsolaki, Johannes R. Streffer, Christoph Hock, Roger M. Nitsch, M. Hasan Mohajeri and Andreas Papassotiropoulos

in Human Molecular Genetics

Volume 13, issue 1, pages 47-52
Published in print January 2004 | ISSN: 0964-6906
Published online January 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg361
Glucocorticoid-related genetic susceptibility for Alzheimer's disease

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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 11β-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.

Journal Article.  3186 words.  Illustrated.

Subjects: Genetics and Genomics

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