Vascular endothelial growth factor gene variability is associated with increased risk for AD.
Converging evidence points to a pivotal role of vascular endothelial growth factor (VEGF) in neuronal protection and a lack of its activity in neurodegenerative disorders. To investigate this possible association, we screened the VEGF gene promoter for various well-known single-nucleotide polymorphisms in a series of 249 consecutively recruited Italian patients with sporadic Alzheimer's disease (AD). Genetic analysis indicated different distributions of two single-nucleotide polymorphisms in the AD population compared with healthy control subjects. In particular, the frequencies of -2578A/A and -1198C/T genotypes were significantly greater in AD patients than in control subjects (23.7 vs 14.7% and 2.8 vs 0%, respectively). The -2578A/A genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype. The risk was significantly increased with respect to various VEGF genotype combinations. In contrast, no difference in serum VEGF levels was detected comparing 96 patients and 49 control subjects. These findings suggest that polymorphisms within the promoter region of the VEGF gene confer greater risk for AD, probably by reducing its neuroprotective effect, and confirm the biological role of VEGF in neurodegenerative processes.
Del Bo
Roberto
R
Department of Neurological Sciences, Dino Ferrari Centre and Centre of Excellence on Neurodegenerative Diseases, University of Milan, I.R.C.C.S. Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy. roberto.delbo@unimi.it
Scarlato
Marina
M
Ghezzi
Serena
S
Martinelli Boneschi
Filippo
F
Fenoglio
Chiara
C
Galbiati
Sara
S
Virgilio
Roberta
R
Galimberti
Daniela
D
Galimberti
Gloria
G
Crimi
Marco
M
Ferrarese
Carlo
C
Scarpini
Elio
E
Bresolin
Nereo
N
Comi
Giacomo P
GP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008967:Molecular Biology / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D012306:Risk; D042442:Vascular Endothelial Growth Factors / Q000097:blood / Q000235:genetics*
D042442:Vascular Endothelial Growth Factors