2Department of Immunology, The Faculty of Life Sciences, Michael Smith Building
3Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran
4Centre for Integrated Genomic Medical Research (CIGMR), Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom
Background: Vascular endothelial growth factor (VEGF) has a key role in angiogene-sis and in transplantation. The level of VEGF is related to the differences in the DNA sequence of its promoter region. Objectives: 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 poly-morphisms and the influence of TNF-α and IL-4 on VEGF production was studied. Methods: VEGF –1154 G/A and –2578 C/A were detected using ARMS-PCR. To de-termine the impact of combinations of these two polymorphisms on VEGF production; PBMCs were stimulated by LPS and VEGF production was measured by ELISA. Re-sults: The combinations of –1154 GG/-2578 CC and –1154 GG/-2578 CA were signifi-cantly associated with higher VEGF production (p<0.0001). Production of VEGF was significantly influenced by TNF-α in individuals who had certain VEGF genotype com-binations. Although VEGF production was dramatically suppressed by IL-4, it was not dependent on VEGF genotype. Conclusions: Since TNF-α has influence on the graft outcome, to avoid allocation of grafts from high TNF-α producer donors to recipients, it might be useful to predict and minimize graft rejection by having prior knowledge of TNF-α and also VEGF genotypes especially -1154 G/A and -2578 C/A VEGF.