CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism

被引：35

作者：

Koelsch, Heike ^{[1
]}

Luetjohann, Dieter ^{[2
]}

Jessen, Frank ^{[1
]}

Popp, Julius ^{[1
]}

Hentschel, Frank ^{[3
]}

Kelemen, Peter ^{[3
]}

Schmitz, Sandra ^{[1
]}

Maier, Wolfgang ^{[1
]}

Heun, Reinhard ^{[4
]}

机构：

[1] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany

[2] Univ Bonn, Inst Clin Biochem & Pharmacol, D-5300 Bonn, Germany

[3] Univ Heidelberg, Div Neuroradiol, Cent Inst Mental Hlth, Fac Clin Med Mannheim, D-6900 Heidelberg, Germany

[4] Univ Birmingham, Div Neurosci, Birmingham B15 2TT, W Midlands, England

来源：

EUROPEAN PSYCHIATRY | 2009年 / 24卷 / 03期

关键词：

Cholesterol; 24S-hydroxylase; Alzheimer's disease; CSF; Cholesterol metabolism; HUMAN APOLIPOPROTEIN-E; TRANSCRIPTION FACTOR; 24-HYDROXYLASE CYP46A1; 24S-HYDROXYLASE GENE; POLYMORPHISM; CELLS; EXPRESSION; ASSOCIATION; HOMEOSTASIS; POPULATION;

D O I：

10.1016/j.eurpsy.2008.12.005

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

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. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：183 / 190

页数：8

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