title: The urokinase-type plasminogen activator polymorphism PLAU_1 is a risk factor for APOE-epsilon4 non-carriers in the Italian Alzheimer's disease population and does not affect the plasma Abeta(1-42) level.
abstract: Sporadic Alzheimer's disease (AD) is the most frequent form of dementia in the elderly. A non-conservative polymorphism in the urokinase-type plasminogen activator gene (PLAU_1=RS2227564) has been analyzed, but data are conflicting on whether it is a risk factor for AD. To clarify whether this genetic variant modifies AD risk in the Italian population, we ran a case-control association study on 192 AD and 126 age-matched controls. We did not find any association between PLAU_1 genotype and AD in the whole AD population, but when we stratified our sample by APOE-epsilon4 status, we found a significant association between PLAU_1 genotype (C/T+T/T) and APOE-epsilon4 negative AD subjects (p=0.02, chi(2)-test). The PLAU_1 genotype did not appear to affect the plasma Abeta42 concentration. Our data support a role for PLAU_1 as an independent genetic risk factor for AD in the Italian population for those subjects who do not have the APOE-epsilon4 allele.
authors.affiliation: Department of Neuroscience, Mario Negri Institute for Pharmacological Research, via Eritrea 62, 20157 Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pesaresi
authors.forename: Sara
authors.initials: S
authors.lastname: Batelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Prato
authors.forename: Letizia
authors.initials: L
authors.lastname: Polito
authors.forename: Carlo
authors.initials: C
authors.lastname: Lovati
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Quadri
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D014568:Urokinase-Type Plasminogen Activator