Association studies between the plasmin genes and late-onset Alzheimer's disease.
The plasmin system is involved in the degradation of Abeta peptides, the accumulation of which in brain is a hallmark of Alzheimer's disease (AD). In a North European case-control AD dataset we studied 14 common variations in the PLG, PAI-1, PLAT and PLI genes encoding components of the plasmin system. Among the four polymorphisms in the PLAT, PAI-1 and PLI genes showing nominally significant evidence for an association with AD (allele p-value=0.01-0.00003) the strongest association was detected for the deletion allele in the Alu-repeat region of the PLAT gene. However, none of these positive results were confirmed in follow-up studies using an independent Canadian case-control cohort and two familial AD datasets of North European and Caribbean Hispanic origin. Thus, the current survey does not support the notion that common polymorphisms in the plasmin genes influence the development of AD.
Shibata
Nobuto
N
Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada.
Kawarai
Toshitaka
T
Meng
Yan
Y
Lee
Joseph H
JH
Lee
Hye-Seung
HS
Wakutani
Yosuke
Y
Shibata
Eri
E
Pathan
Nazia
N
Bi
Andrew
A
Sato
Christine
C
Sorbi
Sandro
S
Bruni
Amalia C
AC
Duara
Ranjan
R
Mayeux
Richard
R
Farrer
Lindsay A
LA
George-Hyslop
Peter St
PS
Rogaeva
Ekaterina
E
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D005192:Family Health; D005260:Female; D005341:Fibrinolysin / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D053829:Amyloid Precursor Protein Secretases; D005341:Fibrinolysin