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Vascular endothelial growth factor gene variability is associated with increased risk for AD
Author(s) -
Del Bo Roberto,
Scarlato Marina,
Ghezzi Serena,
Martinelli Boneschi Filippo,
Fenoglio Chiara,
Galbiati Sara,
Virgilio Roberta,
Galimberti Daniela,
Galimberti Gloria,
Crimi Marco,
Ferrarese Carlo,
Scarpini Elio,
Bresolin Nereo,
Comi Giacomo P.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20390
Subject(s) - genotype , vascular endothelial growth factor , single nucleotide polymorphism , apolipoprotein e , medicine , biology , vegf receptors , disease , gene , risk factor , alzheimer's disease , case control study , neuroprotection , endocrinology , genetics , oncology
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. Ann Neurol 2005;57:373–380