Association study of cholesterol-related genes in Alzheimer's disease.
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.
Wollmer
M Axel
MA
Division of Psychiatry Research, University of Zürich, August Forel Str. 1, 8008 Zurich, Switzerland. awollmer@bli.unizh.ch
Sleegers
Kristel
K
Ingelsson
Martin
M
Zekanowski
Cezary
C
Brouwers
Nathalie
N
Maruszak
Aleksandra
A
Brunner
Fabienne
F
Huynh
Kim-Dung
KD
Kilander
Lena
L
Brundin
Rose-Marie
RM
Hedlund
Marie
M
Giedraitis
Vilmantas
V
Glaser
Anna
A
Engelborghs
Sebastiaan
S
De Deyn
Peter P
PP
Kapaki
Elisabeth
E
Tsolaki
Magdalini
M
Daniilidou
Makrina
M
Molyva
Dimitra
D
Paraskevas
George P
GP
Thal
Dietmar R
DR
Barcikowska
Maria
M
Kuznicki
Jacek
J
Lannfelt
Lars
L
Van Broeckhoven
Christine
C
Nitsch
Roger M
RM
Hock
Christoph
C
Papassotiropoulos
Andreas
A
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
D053327:Apolipoprotein E4; D005819:Genetic Markers; D002784:Cholesterol