VEGF haplotypes are associated with increased risk to progressive supranuclear palsy and corticobasal syndrome.
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are in the spectrum of tauopathies and recognized to have a strong genetic background. It has been widely reported that MAPT tau haplotype H1 is a genetic risk factor in both conditions, but no other genetic determinants have so far been proposed. Recently, vascular endothelial growth factor (VEGF) haplotypes were reported to confer risk to frontotemporal dementia (FTD). The aim of this study was to evaluate the role of VEGF genetic determinants in PSP and CBS susceptibility. We evaluated a cohort of 687 unrelated Italian subjects, including 117 PSP, 108 CBS, 199 FTD, and 263 healthy controls. Genotype and allele frequencies of three well-known polymorphisms located within the VEGF promoter (-2578C/A, -1190G/A, and -1154G/A) were carried out. Genetic analysis revealed the presence of significant changes in terms of genotype and allele distributions in patients compared to healthy controls. A-G-G haplotype (-2578C/A, 1190G/A, -1154G/A) was overrepresented in both PSP (OR=6.64, 95% CI=2.3-19.6, P=0.0003, CGG=reference) and CBS (OR=5.20, 95% CI=1.70-15.9, P=0.003, CGG=reference) compared to healthy subjects. No differences between PSP and CBS and FTD were found, and the A-G-G haplotype was also overrepresented in FTD. Overall, these data suggest that VEGF gene variability represents a susceptibility factor for PSP and CBS. These data argue that additional genes may confer disease risk to PSP and CBS, and to FTD as well, beyond the MAPT tau haplotype. Further studies are warranted.
Borroni
Barbara
B
Department of Neurology, University of Brescia, Centre for Aging Brain and Neurodegenerative Disorders, Brescia, Italy. bborroni@inwind.it
Del Bo
Roberto
R
Goldwurm
Stefano
S
Archetti
Silvana
S
Bonvicini
Cristian
C
Agosti
Chiara
C
Bigni
Barbara
B
Papetti
Alice
A
Ghezzi
Serena
S
Sacilotto
Giorgio
G
Pezzoli
Gianni
G
Gennarelli
Massimo
M
Bresolin
Nereo
N
Comi
Giacomo Pietro
GP
Padovani
Alessandro
A
D000368:Aged; D001480:Basal Ganglia Diseases / Q000209:etiology* / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D057180:Frontotemporal Dementia / Q000097:blood / Q000209:etiology / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013494:Supranuclear Palsy, Progressive / Q000097:blood / Q000209:etiology / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A