title: The influence of immunosuppressive drugs on vascular endothelial growth factor production in relation to VEGF -1154 g and -2578 C genotypes.
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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kerman Physiology Research Centre, Kerman University of Medical Sciences, Kerman, Iran. mozhganmohammadi69@yahoo.co.uk
authors.forename: Mojgan
authors.initials: M
authors.lastname: Mohammadi
authors.forename: Philip J R
authors.initials: PJ
authors.lastname: Day
mesh_terms: D017077:Culture Media, Conditioned / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D042461:Vascular Endothelial Growth Factor A