Correlation between circulating VEGF levels and disease activity in rheumatoid arthritis: a meta-analysis

Objective. To systematically review evidence regarding the relationship between circulating vascular endothelial growth factor (VEGF) levels and rheumatoid arthritis (RA), the correlation between serum VEGF levels and RA activity, and the association between VEGF polymorphisms and RA susceptibility. Methods. We conducted a meta-analysis of the serum/plasma VEGF levels in patients with RA and controls, the correlation coefficients between the circulating VEGF levels and disease activity in patients with RA, and the association between VEGF -2578 A/C, -634 C/G, + 936 T/C, and -1154 A/G polymorphisms and the risk for RA. Results. In total, 13 studies including 2508 patients with RA and 2489 controls were included. Meta-analysis revealed that VEGF level was significantly higher in the RA than in the control group (standard mean difference [SMD] = 1.480, 95% confidence interval [CI] = 0.71-2.241, p = 1.4 x 10-4). Stratification by adjustment for age and gender revealed significantly higher VEGF levels for the adjustment and non-adjustment groups in the RA group (SMD = 1.360, 95% CI = 0.445-2.276, p = 0.004; SMD = 1.557, 95% CI = 0.252-2.861, p = 0.019, respectively). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating VEGF levels and disease activity in RA, and between circulating VEGF and C-reactive protein levels. However, no association was found between RA and the VEGF -2578 A/C, -634 C/G, + 936 T/C, and -1154 A/G polymorphisms. Conclusion. Our meta-analysis revealed significantly higher circulating VEGF levels in patients with RA and a positive correlation between VEGF levels and disease activity in RA, but no association between the VEGF -2578 A/C, -634 C/G,+ 936 T/C, and -1154 A/G polymorphisms and the development of RA.This study was supported in part by a grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI15C2958)