Cluster analysis of risk factor genetic polymorphisms in Alzheimer's disease.
Multiple genetic variants may contribute to the risk of developing Alzheimer's disease. We have analyzed polymorphisms in 9 genes to determine whether particular combinations would contribute to this risk. The genes were APOE, LDLr, CST3, CTSD, TNF, BACE1, MAPT, STH, eNOS, and TFCP2. Three risk groups for the disease were identified. Risk group I was younger, was heterozygous for the CST3 (GA), CTSD2936 (AG), TNF -308 (AG) genetic variants. Risk group II was older, was homozygous for the -427 APOE promoter polymorphism (TT), and heterozygous for the MAPT deletion and for the STH variant (QR). Group III had both the youngest and oldest subjects, were heterozygous for the -863 (AC) and -1031 (CT) TNF promoter polymorphisms. All three groups carried the APOE 4 allele and were heterozygous for both BACE1 polymorphisms. The control groups were carriers of the APOE 3 allele and were homozygous for the BACE1 genetic variants.
Randall
C N
CN
Institute of Molecular Medicine and Genetics (IMMAG), Medical College of Georgia, 1120 15th Street, Augusta, GA, 30912, USA.
Strasburger
D
D
Prozonic
J
J
Morris
S N
SN
Winkie
A D
AD
Parker
G R
GR
Cheng
D
D
Fennell
E M
EM
Lanham
I
I
Vakil
N
N
Huang
J
J
Cathcart
H
H
Huang
R
R
Poduslo
S E
SE
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D002402:Cathepsin D / Q000235:genetics; D016000:Cluster Analysis; D055316:Cystatin C / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C525030:CST3 protein, human; D055316:Cystatin C; D011973:Receptors, LDL; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C533922:CTSD protein, human; D002402:Cathepsin D