Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2.
Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin. Plasmin is involved in processing of amyloid precursor protein and degrades secreted and aggregated amyloid-beta, a hallmark of Alzheimer disease (AD). PLAU, the gene encoding uPA, maps to chromosome 10q22.2 between two regions showing linkage to late-onset AD (LOAD). We genotyped a frequent C/T single nucleotide polymorphism in codon 141 of PLAU (P141L) in 347 patients with LOAD and 291 control subjects. LOAD was associated with homozygous C/C PLAU genotype in the whole sample (chi2=15.7, P=0.00039, df 2), as well as in all sub-samples stratified by gender or APOE epsilon4 carrier status (chi2> or = 6.84, P< or =0.033, df 2). Odds ratio for LOAD due to homozygosity C/C was 1.89 (95% confidence interval 1.37-2.61). PLAU is a promising new candidate gene for LOAD, with allele C (P141) being a recessive risk allele or allele T (L141) conferring protection.
Finckh
U
U
Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. finckh@uke.uni-hamburg.de
van Hadeln
K
K
Müller-Thomsen
T
T
Alberici
A
A
Binetti
G
G
Hock
C
C
Nitsch
R M
RM
Stoppe
G
G
Reiss
J
J
Gal
A
A
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D002879:Chromosomes, Human, Pair 10; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator