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VEGF gene variability and type 1 diabetes: evidence for a protective role
Authors:Roberto Del Bo  Marina Scarlato  Serena Ghezzi  Anna Maestroni  Lisa Sjölind  Carol Forsblom  Maija Wessman  Per-Henrik Groop  Giacomo Pietro Comi  Nereo Bresolin  Livio Luzi  Gianpaolo Zerbini
Affiliation:(1) Department of Neurological Sciences, Centro Dino Ferrari, University of Milan, Milan, Italy;(2) I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy;(3) Renal Pathophysiology of Diabetes Unit, Section Nutrition-Metabolism, Department of Medicine, San Raffaele Scientific Institute, Milan, Italy;(4) FinnDiane Study Group, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland;(5) Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland;(6) Finnish Genome Center, University of Helsinki, Helsinki, Finland
Abstract:Vascular endothelial growth factor (VEGF) is a multifunctional cytokine originally described as an angiogenic factor. A number of reports have recently demonstrated that VEGF increases pancreatic islet survival after islet transplantation by stimulating angiogenesis and improving islet revascularization. Whether VEGF can protect from the autoimmune destruction of insulin-producing beta-cells that characterizes the development of type 1 diabetes is presently unknown. To clarify this issue, we studied the association of three polymorphisms of the promoter region of VEGF with type 1 diabetes in the Italian and the Finnish populations. The polymorphisms considered [C(-2578)A, G(-1190)A, and G(-1154)A] are known to modulate in vitro and in vivo VEGF expression. We found that VEGF promoter genotypes are associated with type 1 diabetes in both populations, but with different combinations. In Italian individuals, the -2578AA and -1190AA genotypes are associated with type 1 diabetes and accelerate its onset, while in Finnish individuals, -1154GG and -1190GG protect from type 1 diabetes and delay its onset. In conclusion, because the expected functional consequence of both genotype combinations is a reduced VEGF expression in diabetic patients, we propose a protective role of VEGF in the development of type 1 diabetes.
Keywords:Human  Type 1 diabetes  Cytokines  Tolerance
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