CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism - 06/04/09
, Dieter Lütjohann b, Frank Jessen a, Julius Popp a, Frank Hentschel c, Peter Kelemen c, Sandra Schmitz a, Wolfgang Maier a, Reinhard Heun d
Corresponding author. Unikliniken Bonn, Klinik fur Psychiatrie und Psychotherapie, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Tel.: +49 228 287 19398; fax: +49 228 287 16383.Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Cholesterol 24S-hydroxylase, Alzheimer's disease, CSF, Cholesterol metabolism
Plan
Vol 24 - N° 3
P. 183-190 - avril 2009 Retour au numéro
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