Vascular endothelial growth factor production is regulated by gene polymorphisms

ABSTRACT

Vascular endothelial growth factor [VEGF] has a key role in angiogenesis and in transplantation. The level of VEGF is related to the differences in the DNA sequence of its promoter region. In this study, the association between the combination of VEGF -1154 G and -2578 C alleles and VEGF production by LPS-stimulated PBMCs was investigated. In addition; the relationship between VEGF polymorphisms and the influence of TNF-alpha and IL-4 on VEGF production was studied. VEGF -1154 G/A and -2578 C/A were detected using ARMS-PCR. To determine the impact of combinations of these two polymorphisms on VEGF production; PBMCs were stimulated by LPS and VEGF production was measured by ELISA. The combinations of -1154 GG/-2578 CC and -1154 GG/-2578 CA were significantly associated with higher VEGF production [p<0.0001]. Production of VEGF was significantly influenced by TNF-alpha in individuals who had certain VEGF genotype combinations. Although VEGF production was dramatically suppressed by IL-4, it was not dependent on VEGF genotype. Since TNF-alpha has influence on the graft outcome, to avoid allocation of grafts from high TNF-alpha producer donors to recipients, it might be useful to predict and minimize graft rejection by having prior knowledge of TNF-alpha and also VEGF genotypes especially -1154 G/A and -2578 C/A VEGF