Focus on Alzheimer's Disease and Related Disorders: A Cluster of Cholesterol-Related Genes Confers Susceptibility for Alzheimer's Disease
J Clin Psychiatry 2005;66(7):940-947
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Objective: Polygenic diseases are related to the
complex interplay of genetic variations. We evaluated whether
clusters of cholesterol- and lipid-related genetic variations are
associated with Alzheimer's disease.
Method: We analyzed 12 cholesterol-related
single nucleotide polymorphisms and 48 control polymorphisms in
545 study participants (Alzheimer's disease group N = 284; control
group N = 261). Diagnoses of Alzheimer's disease were made
according to the NINCDS-ADRDA criteria. Multi-locus genetic
association analysis was done with the set-association method.
Dates of data collection were from January 2000 to December 2003.
Results: We identified a cluster of
polymorphisms in APOE, SOAT1, APOE 5'-untranslated region, OLR1, CYP46A1, LPL, LIPA, and APOA4 conferring
significant (p = .0002) susceptibility for Alzheimer's disease.
This gene cluster reached a diagnostic accuracy of 74% and
correlated significantly (p = .018) with the levels of the brain
cholesterol catabolite 24S-hydroxycholesterol in the
Conclusion: Our results establish a novel
approach for the identification of disease-related genetic
clusters and demonstrate the need for multi-locus methods in the
genetics of complex diseases.