Glucocorticoid-related genetic susceptibility for Alzheimer's disease - PubMed (original) (raw)
Comparative Study
. 2004 Jan 1;13(1):47-52.
doi: 10.1093/hmg/ddg361. Epub 2003 Oct 28.
Affiliations
- PMID: 14583441
- DOI: 10.1093/hmg/ddg361
Free article
Comparative Study
Glucocorticoid-related genetic susceptibility for Alzheimer's disease
Dominique J-F de Quervain et al. Hum Mol Genet. 2004.
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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.
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