title: Association study of cholesterol-related genes in Alzheimer's disease.
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 < or = 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.
authors: Division of Psychiatry Research, University of Zürich, August Forel Str. 1, 8008 Zurich, Switzerland. awollmer@bli.unizh.ch
authors: M Axel
authors: MA
authors: Wollmer
authors: Kristel
authors: K
authors: Sleegers
authors: Martin
authors: M
authors: Ingelsson
authors: Cezary
authors: C
authors: Zekanowski
authors: Nathalie
authors: N
authors: Brouwers
authors: Aleksandra
authors: A
authors: Maruszak
authors: Fabienne
authors: F
authors: Brunner
authors: Kim-Dung
authors: KD
authors: Huynh
authors: Lena
authors: L
authors: Kilander
authors: Rose-Marie
authors: RM
authors: Brundin
authors: Marie
authors: M
authors: Hedlund
authors: Vilmantas
authors: V
authors: Giedraitis
authors: Anna
authors: A
authors: Glaser
authors: Sebastiaan
authors: S
authors: Engelborghs
authors: Peter P
authors: PP
authors: De Deyn
authors: Elisabeth
authors: E
authors: Kapaki
authors: Magdalini
authors: M
authors: Tsolaki
authors: Makrina
authors: M
authors: Daniilidou
authors: Dimitra
authors: D
authors: Molyva
authors: George P
authors: GP
authors: Paraskevas
authors: Dietmar R
authors: DR
authors: Thal
authors: Maria
authors: M
authors: Barcikowska
authors: Jacek
authors: J
authors: Kuznicki
authors: Lars
authors: L
authors: Lannfelt
authors: Christine
authors: C
authors: Van Broeckhoven
authors: Roger M
authors: RM
authors: Nitsch
authors: Christoph
authors: C
authors: Hock
authors: Andreas
authors: A
authors: Papassotiropoulos
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D002784:Cholesterol / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
chemical_list: D053327:Apolipoprotein E4; D005819:Genetic Markers; D002784:Cholesterol