CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism.
Détails
ID Serval
serval:BIB_2FD1C826DBB5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism.
Périodique
European Psychiatry : the Journal of the Association of European Psychiatrists
ISSN
0924-9338 (Print)
ISSN-L
0924-9338
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
24
Numéro
3
Pages
183-190
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
BACKGROUND: Cholesterol 24S-hydroxylase (CYP46) catalyzes the conversion of cholesterol to 24S-hydroxycholesterol, the primary cerebral cholesterol elimination product. Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer's disease (AD) and results are contradictory.
METHODS: We performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.
RESULTS: Two of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p=0.016; rs4900442: p=0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p=0.006). Haplotypes including both SNPs were calculated and haplotype G-C was identified to influence the risk of AD (p=0.005). AD patients and non-demented controls, who were carriers of the G-C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p=0.001) and cholesterol (p<0.001).
CONCLUSION: Our results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.
METHODS: We performed a gene variability screening in CYP46A1 and investigated the effect of gene variants on the risk of AD and on CSF levels of cholesterol and 24S-hydroxycholesterol.
RESULTS: Two of the identified 16 SNPs in CYP46A1 influenced AD risk in our study (rs7157609: p=0.016; rs4900442: p=0.019). The interaction term of both SNPs was also associated with an increased risk of AD (p=0.006). Haplotypes including both SNPs were calculated and haplotype G-C was identified to influence the risk of AD (p=0.005). AD patients and non-demented controls, who were carriers of the G-C haplotype, presented with reduced CSF levels of 24S-hydroxycholesterol (p=0.001) and cholesterol (p<0.001).
CONCLUSION: Our results suggest that CYP46A1 gene variations might act as risk factor for AD via an influence on brain cholesterol metabolism.
Mots-clé
Aged, Aged, 80 and over, Alzheimer Disease/cerebrospinal fluid, Alzheimer Disease/genetics, Amyloid beta-Peptides/metabolism, Brain/metabolism, Cholesterol/cerebrospinal fluid, Cholesterol/genetics, Female, Genetic Predisposition to Disease/genetics, Genetic Variation, Haplotypes/genetics, Humans, Hydroxycholesterols/cerebrospinal fluid, Hydroxycholesterols/metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide/genetics, Risk Factors, Steroid Hydroxylases/genetics, Steroid Hydroxylases/metabolism
Pubmed
Création de la notice
29/10/2012 11:45
Dernière modification de la notice
20/08/2019 14:14
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