title: VEGF haplotypes are associated with increased risk to progressive supranuclear palsy and corticobasal syndrome.
abstract: 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.
authors.affiliation: Department of Neurology, University of Brescia, Centre for Aging Brain and Neurodegenerative Disorders, Brescia, Italy. bborroni@inwind.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.forename: Chiara
authors.initials: C
authors.lastname: Agosti
authors.forename: Barbara
authors.initials: B
authors.lastname: Bigni
authors.forename: Alice
authors.initials: A
authors.lastname: Papetti
authors.forename: Serena
authors.initials: S
authors.lastname: Ghezzi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sacilotto
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: 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*
chemical_list: D042461:Vascular Endothelial Growth Factor A