title: Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an "angiogenic disease" because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA.
  
  
  OBJECTIVE
  The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA.
  
  
  METHODS
  581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA.
  
  
  RESULTS
  The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was lower than the number of women with wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher in RA patients than in control groups (both p = 0,0001).
  
  
  CONCLUSIONS
  Present findings indicated that VEGF genetic polymorphism as well as VEGF protein levels may be associated with the susceptibility to RA in the Polish population.
authors: Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors: Agnieszka
authors: A
authors: Paradowska-Gorycka
authors: Department of Physiology, Pomeranian Medical University, Szczecin, Poland.
authors: Andrzej
authors: A
authors: Pawlik
authors: Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors: Katarzyna
authors: K
authors: Romanowska-Prochnicka
authors: Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.|Department of Pathophysiology, Warsaw Medical University, Warsaw, Poland.
authors: Ewa
authors: E
authors: Haladyj
authors: Department of Pharmacology, Pomeranian Medical University, Szczecin, Poland.
authors: Damian
authors: D
authors: Malinowski
authors: Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors: Barbara
authors: B
authors: Stypinska
authors: Department of Gerontology and Public Health, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors: Malgorzata
authors: M
authors: Manczak
authors: Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors: Marzena
authors: M
authors: Olesinska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A