<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

Distribution of genotypes and allele frequencies of <i>FLT-1</i> SNPs among patients with RA and healthy subjects (p = RA vs controls).

<p>Distribution of genotypes and allele frequencies of <i>FLT-1</i> SNPs among patients with RA and healthy subjects (p = RA vs controls).</p

Correlation of FLT-1 protein concentration of the various clinical parameters (RA).

<p>Correlation of FLT-1 protein concentration of the various clinical parameters (RA).</p

Clinical characteristics RA patients with CVD.

<p>Clinical characteristics RA patients with CVD.</p

Demographic and clinical characteristics of RA patients.

<p>Demographic and clinical characteristics of RA patients.</p

Variation in sFLT-1 serum levels in RA patients and controls in relation to FLT-1 gene polymorphisms.

<p>Variation in sFLT-1 serum levels in RA patients and controls in relation to FLT-1 gene polymorphisms.</p

Linkage disequilibrium (LD) map of FLT-1 gene polymorphisms.

<p>Linkage disequilibrium (LD) map of FLT-1 gene polymorphisms.</p