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01-08-2007 | Original Article

Association study of cholesterol-related genes in Alzheimer’s disease

Authors: M. Axel Wollmer, Kristel Sleegers, Martin Ingelsson, Cezary Zekanowski, Nathalie Brouwers, Aleksandra Maruszak, Fabienne Brunner, Kim-Dung Huynh, Lena Kilander, Rose-Marie Brundin, Marie Hedlund, Vilmantas Giedraitis, Anna Glaser, Sebastiaan Engelborghs, Peter P. De Deyn, Elisabeth Kapaki, Magdalini Tsolaki, Makrina Daniilidou, Dimitra Molyva, George P. Paraskevas, Dietmar R. Thal, Maria Barcikowska, Jacek Kuznicki, Lars Lannfelt, Christine Van Broeckhoven, Roger M. Nitsch, Christoph Hock, Andreas Papassotiropoulos

Published in: Neurogenetics | Issue 3/2007

Abstract

Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.

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Title: Association study of cholesterol-related genes in Alzheimer’s disease
Authors: M. Axel Wollmer
Kristel Sleegers
Martin Ingelsson
Cezary Zekanowski
Nathalie Brouwers
Aleksandra Maruszak
Fabienne Brunner
Kim-Dung Huynh
Lena Kilander
Rose-Marie Brundin
Marie Hedlund
Vilmantas Giedraitis
Anna Glaser
Sebastiaan Engelborghs
Peter P. De Deyn
Elisabeth Kapaki
Magdalini Tsolaki
Makrina Daniilidou
Dimitra Molyva
George P. Paraskevas
Dietmar R. Thal
Maria Barcikowska
Jacek Kuznicki
Lars Lannfelt
Christine Van Broeckhoven
Roger M. Nitsch
Christoph Hock
Andreas Papassotiropoulos
Publication date: 01-08-2007
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 3/2007
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-007-0087-z

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Association study of cholesterol-related genes in Alzheimer’s disease

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