Background/Purpose:   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 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 receptor 2 (VEGFR2; KDR) is the earliest marker for endothelial cell development, it is considered a crucial signal transducer in angiogenesis. And therefore is involved in the development of inflammation. VEGFA is the one of most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA. The aim of the study was to identify functional KDR variants and their possible association with KDR expression, susceptibility to and severity of RA.

Methods:  641 RA patients and of 340 healthy individuals were examined for +1416A/T KDR gene polymorphisms by PCR-RFLP method and for +889G/A and -604 T/C KDR gene polymorphisms by TaqMan SNP genotyping assay. Serum KDR levels in RA patients and controls were measured by ELISA.

Results:   The +1416A/T KDR gene polymorphism under the codominant and recessive (AA+AT vs TT) models were associated with RA (p=0.02; p=0.019, respectively). The +889 G/A KDR gene polymorphism under the dominant (GG vs GA+AA) model was associated with RA (p=0.005). Furthermore, KDR -604 T/C revealed differences in the case-control distribution in codominant and dominant models (all p<0.0001). The genotype-phenotype analysis showed significant association between the KDR+889G/A and Larsen score (p=0.03), VAS score (p=p<000.1), DAS-28 score (p=p<0.0001), HAQ sore (p=0.02), number of swollen joints (p<0.0001), mean value of ESR (p=0.006), mean value of CRP (p<0.0001), and mean value of creatinine (p=0.02). Additionally the number of women with the polymorphic allele +889 A was higher than the number of women with wild type allele -+889 G (p<0.0001). Serum KDR levels were significantly higher in RA patients than in control groups (p=0.002).

Conclusion:   Present findings indicated that KDR genetic polymorphism may be associated with the susceptibility to and severity of RA in the Polish population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-between-kdr-vegfr2-gene-polymorphisms-and-serum-kdr-protein-levels-in-patients-with-rheumatoid-arthritis/