VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis

Abstract

BackgroundOur study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA).Material/MethodsClinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded.ResultsThe genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05).ConclusionsOur study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA.

KDR (VEGFR2) Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis

“…Also, several genetic variants located in the VEGF-A gene have shown associations with rheumatoid arthritis, cancer, coronary artery disease, and chronic obstructive pulmonary disease. The rs1570360, rs699947, rs2010963, rs833070, and rs3025030 VEGF gene polymorphisms were associated with RA [23,47], cancer [48,49,50,51,52], heart disease [53], chronic obstructive pulmonary disease [54,55], or type 2 diabetes [56]. While the VEGF-C gene polymorphisms were not examined in patients with RA, they were examined in patients with cancer and Kawasaki disease.…”

The VEGFA ‐1154G/A polymorphism is associated with reduced risk of rheumatoid arthritis but not with systemic lupus erythematosus in Mexican women

“…In patients with RA and SLE, circulating VEGF levels are correlated with disease activity (or with synovial lesions) . However, few studies have evaluated the impact of VEGFA polymorphisms on the susceptibility to RA . Moreover, to our knowledge, only two studies have investigated the associations between some VEGFA polymorphisms and susceptibility to SLE .…”

“…7,8 However, few studies have evaluated the impact of VEGFA polymorphisms on the susceptibility to RA. [9][10][11][12][13][14][15][16] Moreover, to our knowledge, only two studies have investigated the associations between some VEGFA polymorphisms and susceptibility to SLE. 17,18 For example, in patients from Russia and Poland, the VEGFA -2578G/A SNP was found to be associated with RA susceptibility.…”

“…2,4,7,8 On the other hand, single nucleotide polymorphisms (SNPs) located in VEGFA, including rs699947 (-2578C/A), rs833070G/A (intron 2) and rs3025030G/C (intron 5), have been associated with RA susceptibility, RA activity or synovial lesions. [9][10][11][12][13] However, those findings have not been replicated in all populations studied. 14,15 By contrast, other SNPs in VEGFA, including -634G/A (also known as +405), have not been associated with RA.…”

“…Indeed, circulating VEGF levels were significantly positively correlated with disease activity in RA (or with synovial lesions) and SLE . On the other hand, single nucleotide polymorphisms (SNPs) located in VEGFA, including rs699947 (‐2578C/A), rs833070G/A (intron 2) and rs3025030G/C (intron 5), have been associated with RA susceptibility, RA activity or synovial lesions . However, those findings have not been replicated in all populations studied .…”