RXRA gene variations influence Alzheimer's disease risk and cholesterol metabolism.

Détails

ID Serval
serval:BIB_28A8D2EEBF99
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
RXRA gene variations influence Alzheimer's disease risk and cholesterol metabolism.
Périodique
Journal of Cellular and Molecular Medicine
Auteur⸱e⸱s
Kölsch H., Lütjohann D., Jessen F., Popp J., Hentschel F., Kelemen P., Friedrichs S., Maier T.A., Heun R.
ISSN
1582-4934 (Electronic)
ISSN-L
1582-1838
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
13
Numéro
3
Pages
589-598
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Cholesterol metabolism is altered in Alzheimer's disease (AD). The nuclear hormone receptor Retinoic X Receptor a (RXRa) is a member of the nuclear ligand-activated transcription factor family. RXRs are key regulators of cholesterol synthesis and thus cholesterol metabolism. We performed a systematic screen for gene variants in the RXRA gene. The effect of these gene variants on the risk of AD was investigated in 405 AD patients (mean age: 74.27 +/- 9.37 years; female 78.6%) and 347 controls (mean age: 73.26 +/- 8.37 years; female 57.2%). Furthermore, the influence of RXRA gene variants on CSF and plasma levels of cholesterol, lathosterol and 24S-hydroxycholesterol were evaluated. One of the identified seven SNPs in RXRA influenced AD risk in our single marker analysis (rs3132293: P= 0.006). Haplotype analysis identified a three-marker haplotype (TGC) consisting of rs3118570, rs1536475 and rs3132293, which decreased the risk of AD (P= 0.009). The single marker rs3132293 (P= 0.026) and the TGC haplotype (P= 0.026) influenced CSF lathosterol levels in non-demented controls, and cholesterol levels in the combined sample comprising AD patients and controls (Rs3132293: P= 0.050; TGC haplotype: P= 0.035). 24S-Hydroxycholesterol CSF and plasma levels were also influenced by rs3132293 (CSF: P= 0.004; plasma: P= 0.001) and the TGC haplotype (CSF: P= 0.004; plasma: P= 0.002); this effect was most pronounced in AD patients (rs3132293: CSF: P= 0.009, plasma: P= 0.002; TGC haplotype: CSF: P= 0.019, plasma: P= 0.005). Our results suggest that RXRA gene variants might act as risk factor for AD via an influence on cerebral cholesterol metabolism.
Mots-clé
Aged, Aged, 80 and over, Alzheimer Disease/blood, Alzheimer Disease/cerebrospinal fluid, Case-Control Studies, Cholesterol/blood, Cholesterol/metabolism, Female, Gene Frequency, Genetic Markers, Genetic Predisposition to Disease, Haplotypes, Humans, Linkage Disequilibrium/genetics, Male, Middle Aged, Polymorphism, Single Nucleotide/genetics, Retinoid X Receptor alpha/genetics
Pubmed
Création de la notice
29/10/2012 10:48
Dernière modification de la notice
20/08/2019 13:08
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