VEGF gene variability and type 1 diabetes: evidence for a protective role.
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.
Del Bo
Roberto
R
Department of Neurological Sciences, Centro Dino Ferrari, University of Milan, Milan, Italy.
Scarlato
Marina
M
Ghezzi
Serena
S
Maestroni
Anna
A
Sjölind
Lisa
L
Forsblom
Carol
C
Wessman
Maija
M
Groop
Per-Henrik
PH
Comi
Giacomo Pietro
GP
Bresolin
Nereo
N
Luzi
Livio
L
Zerbini
Gianpaolo
G
D000328:Adult; D017668:Age of Onset; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005387:Finland; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A