<i>FLT-1</i> gene polymorphisms and protein expression profile in rheumatoid arthritis

<div><p>Objectives</p><p>Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the <i>FLT-1</i> polymorphisms with different “angiogenic diseases” suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify <i>FLT-1</i> genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA.</p><p>Methods</p><p>The <i>FLT-1</i> gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated.</p><p>Results</p><p>The <i>FLT-1</i> gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the <i>FLT-1</i> rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D’ = 0.97 and r2 = 0.83. The <i>FLT-1</i> rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, <i>FLT-1</i> genetic variants conferred higher sFLT-1 levels in RA patients compared to controls.</p><p>Conclusion</p><p><i>FLT-1</i> rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.</p></div

Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis

<div><p>Background</p><p>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.</p><p>Objectives</p><p>The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA.</p><p>Methods</p><p>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.</p><p>Results</p><p>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).</p><p>Conclusion</p><p>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.</p></div

The disease activity and laboratory parameters in relation to <i>VEGF</i>-1154 A/G; recessive model.

<p>The disease activity and laboratory parameters in relation to <i>VEGF</i>-1154 A/G; recessive model.</p

Correlation of VEGF protein expression level with the various clinical characteristics in RA.

<p>Correlation of VEGF protein expression level with the various clinical characteristics in RA.</p

Demographic and clinical characteristics of the RA patients with CVD and without CVD.

<p>Demographic and clinical characteristics of the RA patients with CVD and without CVD.</p

Distribution of genotypes and allele frequencies of VEGF SNPs among Polish patients with RA and healthy subjects.

<p>OR adjusted for sex and age.</p

<i>VEGF</i> haplotypes in rheumatoid arthritis (RA) patients and controls.

<p><i>VEGF</i> haplotypes in rheumatoid arthritis (RA) patients and controls.</p