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Neurogenetics

, Volume 8, Issue 3, pp 179–188 | Cite as

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

  • 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
Original Article

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.

Keywords

HMGCS2 FDPS NPC2 ABCG1 Polymorphism 

Notes

Acknowledgments

We thank Ms. Esmeralda Gruber and Ms. Christin Wilde for patient care and sampling. This work was supported by grants of the Hartmann Müller-Stiftung für Medizinische Forschung to M. A. W. (983), of the Julius Klaus-Stiftung to M. A. W and A.P., by the Swiss National Science Foundation (PP00B-68859) and the Novartis Stiftung to A. P., by the National Center for Competence in Research (NCCR) “Neuronal Plasticity and Repair”, by the Polish Ministry of Science (PBZ-KBN-124/P05/2004), by the Fund of Scientific Research-Flanders (FWO-F), and by the EU APOPIS program (contract LSHM-CT-2003-503330). K. S. is a postdoctoral fellow and N. B. a doctoral fellow of the FWO-F. The study complies with the current law of the countries in which it was performed.

Supplementary material

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. Axel Wollmer
    • 1
  • Kristel Sleegers
    • 2
  • Martin Ingelsson
    • 3
  • Cezary Zekanowski
    • 4
  • Nathalie Brouwers
    • 2
  • Aleksandra Maruszak
    • 4
  • Fabienne Brunner
    • 1
  • Kim-Dung Huynh
    • 1
  • Lena Kilander
    • 3
  • Rose-Marie Brundin
    • 3
  • Marie Hedlund
    • 3
  • Vilmantas Giedraitis
    • 3
  • Anna Glaser
    • 3
  • Sebastiaan Engelborghs
    • 5
    • 6
  • Peter P. De Deyn
    • 5
    • 6
  • Elisabeth Kapaki
    • 7
  • Magdalini Tsolaki
    • 8
  • Makrina Daniilidou
    • 8
  • Dimitra Molyva
    • 8
  • George P. Paraskevas
    • 7
  • Dietmar R. Thal
    • 9
  • Maria Barcikowska
    • 4
  • Jacek Kuznicki
    • 10
  • Lars Lannfelt
    • 3
  • Christine Van Broeckhoven
    • 2
  • Roger M. Nitsch
    • 1
  • Christoph Hock
    • 1
  • Andreas Papassotiropoulos
    • 1
    • 11
  1. 1.Division of Psychiatry ResearchUniversity of ZürichZurichSwitzerland
  2. 2.Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Laboratory of NeurogeneticsInstitute Born-Bunge and University of AntwerpAntwerpBelgium
  3. 3.Department of Public Health/GeriatricsUppsala UniversityUppsalaSweden
  4. 4.Department of Neurodegenerative Disorders, Medical Research CenterPolish Academy of SciencesWarsawPoland
  5. 5.Laboratory of Neurochemistry and Behavior, Institute Born-BungeUniversity of AntwerpAntwerpBelgium
  6. 6.Memory Clinic, Division of NeurologyMiddelheim General Hospital AntwerpAntwerpBelgium
  7. 7.Department of NeurologyAthens National UniversityAthensGreece
  8. 8.Third Department of NeurologyAristotle University of ThessalonikiThessalonikiGreece
  9. 9.Department of NeuropathologyUniversity of BonnBonnGermany
  10. 10.Laboratory of NeurodegenerationInternational Institute of Molecular and Cell Biology in Warsaw and Nencki Institute of Experimental BiologyWarsawPoland
  11. 11.Division of Molecular Psychology and BiozentrumUniversity of BaselBaselSwitzerland

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