Abstract
ObjectivesInflammation 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 FLT-1 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 FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA.MethodsThe FLT-1 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.ResultsThe FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 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 FLT-1 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, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls.ConclusionFLT-1 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.
Highlights
Rheumatoid arthritis (RA) is the one of the most common, polygenic, autoimmune diseases
The fms-related tyrosine kinase 1 (FLT-1) gene polymorphisms showed no significant differences in the proportion of cases and controls
FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls
Summary
Rheumatoid arthritis (RA) is the one of the most common, polygenic, autoimmune diseases. The process of new vessels formation is regulated by many mediators, of which the central and the best characterized are vascular endothelial growth factor (VEGF) family and its receptors [4]. VEGF plays a role as a functional bridge between inflammation and angiogenesis [7]. VEGFR-1 expression is not limited to the vascular endothelial cells. This expression induces abnormally high angiogenesis [8,9,10]. VEGFR-1 has a central role in pathological angiogenesis during RA, mediated by VEGF, and by placenta growth factor (PlGF) [11]. An improved understanding of RA molecular pathogenesis will enable the development of new intervention strategies
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