Mojgan Mohammadi; Philip J.R. Day
Volume 7, Issue 4 , December 2010, , Pages 217-225
Abstract
Background: The pathogenesis of many diseases is correlated to irregularity in vascular endothelial growth factor (VEGF) expression. Results from several association studies show that variation in the level of VEGF expression is related to polymorphic sequences within the VEGF gene. Additionally, there ...
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Background: The pathogenesis of many diseases is correlated to irregularity in vascular endothelial growth factor (VEGF) expression. Results from several association studies show that variation in the level of VEGF expression is related to polymorphic sequences within the VEGF gene. Additionally, there are many studies showing that some gene polymorphisms significantly influence the pharmacokinetics of immunosuppressive drugs. Objective: The aim of this study was to determine the influence of immunosuppressive drugs on VEGF production in individuals with different VEGF genotypes. Methods: ARMS-PCR was used to genotype VEGF polymorphisms at positions -1154 and -2578 within the promoter of VEGF gene. A VEGF-specific ELISA was used to determine the influence of immunosuppressive drugs on VEGF production in PBMCs of individuals with different VEGF genotypes. Results: Suppressive effect of mycophenolic acid was observed just in individuals with GG -1154/CC -2578, GG -1154/CA -2578 and GA -1154/CC -2578 haplotypes. Additionally, VEGF was significantly suppressed in all individuals after treatment with rapamycin except those who had AA -1154/CA -2578 and AA -1154/AA -2578 VEGF genotype combinations. Conclusion: Results of a recent study revealed that MMF treatment might be effective in preventing chronic renal rejection only in recipients with IL-10 high producer genotype. Additionally result of another study showed that CYP3A5 genotype markedly influences the pharmacokinetics of rapamycin in kidney transplant recipients. Therefore with regard to our results, different suppressive effect of mycophenolic acid and rapamycin on VEGF production might also be dependent on VEGF genotype.
Mojgan Mohammadi; Mohammad Reza Bazrafshani; Philip.J Day; William. E.R. Ollier
Volume 6, Issue 3 , September 2009, , Pages 119-129
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 ...
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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.