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VEGF gene variability and type 1 diabetes: evidence for a protective role

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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.

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Acknowledgements

We would like to thank the whole Finnish Diabetic Nephropathy Study Group (see reference Pettersson-Fernholm et al. 2004 for details). We are also indebted to Ms. Daniela Gabellini for technical assistance. This work was supported in part by the Folkhälsan Research Foundation, Samfundet Folkhälsan, the Research Funds of the Helsinki University Central Hospital, the Wilhelm and Else Stockmann Foundation, the Sigrid Juselius Foundation, the Academy of Finland (00213 to M.W.), European Commission (contract nr. QLG2-CT-2001-01669), and the Liv och Hälsa Foundation. Finally, we declare that the experiments performed in this study comply with current Italian and Finnish laws.

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Authors and Affiliations

  1. Department of Neurological Sciences, Centro Dino Ferrari, University of Milan, Milan, Italy

    Roberto Del Bo, Marina Scarlato, Serena Ghezzi, Giacomo Pietro Comi & Nereo Bresolin

  2. I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy

    Roberto Del Bo, Marina Scarlato, Serena Ghezzi, Giacomo Pietro Comi & Nereo Bresolin

  3. Renal Pathophysiology of Diabetes Unit, Section Nutrition-Metabolism, Department of Medicine, San Raffaele Scientific Institute, Milan, Italy

    Anna Maestroni, Livio Luzi & Gianpaolo Zerbini

  4. FinnDiane Study Group, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland

    Lisa Sjölind, Carol Forsblom, Maija Wessman & Per-Henrik Groop

  5. Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland

    Lisa Sjölind, Carol Forsblom, Maija Wessman & Per-Henrik Groop

  6. Finnish Genome Center, University of Helsinki, Helsinki, Finland

    Maija Wessman

Authors
  1. Roberto Del Bo
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  2. Marina Scarlato
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  3. Serena Ghezzi
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  4. Anna Maestroni
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  5. Lisa Sjölind
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  6. Carol Forsblom
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  7. Maija Wessman
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  8. Per-Henrik Groop
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  9. Giacomo Pietro Comi
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  10. Nereo Bresolin
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  11. Livio Luzi
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  12. Gianpaolo Zerbini
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Correspondence to Gianpaolo Zerbini.

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Del Bo, R., Scarlato, M., Ghezzi, S. et al. VEGF gene variability and type 1 diabetes: evidence for a protective role. Immunogenetics 58, 107–112 (2006). https://doi.org/10.1007/s00251-006-0089-2

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  • DOI: https://doi.org/10.1007/s00251-006-0089-2

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