Document Type: Original Article

Authors

1 Departments of Immunology

2 Department of Immunology, The Faculty of Life Sciences, Michael Smith Building

3 Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran

4 Centre for Integrated Genomic Medical Research (CIGMR), Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom

Abstract

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.

Keywords