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

Korrelation zwischen dem Spiegel des zirkulierenden vaskulären endothelialen Wachstumsfaktors und Krankheitsaktivität bei rheumatoider Arthritis: eine Metaanalyse

Abstract

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 × 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.

Zusammenfassung

Ziel der Arbeit

Ziel war eine systematische Übersicht über die Evidenz für eine Beziehung zwischen den Werten für den zirkulierenden vaskulären endothelialen Wachstumsfaktor (VEGF) und rheumatoider Arthritis (RA), die Korrelation zwischen Serum-VEGF-Werten und RA-Aktivität sowie den Zusammenhang zwischen VEGF-Polymorphismen und der Suszeptibilität für RA.

Methoden

Die Autoren führten eine Metaanalyse durch zu den Serum-/Plasma-VEGF-Werten bei Patienten mit RA und Kontrollen, zu den Korrelationskoeffizienten zwischen den Spiegeln des zirkulierenden VEGF und der Krankheitsaktivität bei Patienten mit RA und zu dem Zusammenhang zwischen den VEGF-Polymorphismen −2578 A/C, −634 C/G, +936 T/C und −1154 A/G und dem Risiko für eine RA.

Ergebnisse

Insgesamt wurden 13 Studien mit 2508 RA-Patienten und 2489 Kontrollen in die Auswertung einbezogen. Die Metaanalyse ergab, dass der VEGF-Wert in der RA-Gruppe signifikant höher war als in der Kontrollgruppe (Standardmittelwertdifferenz, „standard mean difference“, SMD: 1,480; 95%-Konfidenzintervall, 95%-KI: 0,71–2,241; p = 1,4 × 10−4). Die Stratifizierung unter Berücksichtigung des Alters und Geschlechts erbrachte in der RA-Gruppe signifikant höhere VEGF-Werte für die Gruppen mit und ohne Adjustierung als bei den Kontrollen (SMD: 1,360; 95%-KI: 0,445–2,276; p = 0,004 bzw. SMD: 1,557; 95%-KI: 0,252–2,861; p = 0,019). Die Metaanalyse der Korrelationskoeffizienten zeigte eine signifikant positive Korrelation zwischen den Werten für den zirkulierenden VEGF und der Krankheitsaktivität bei RA sowie zwischen den Spiegeln des zirkulierenden VEGF und den Werten für C‑reaktives Protein. Es wurde jedoch kein Zusammenhang zwischen RA und den VEGF-Polymorphismen −2578 A/C, −634 C/G, +936 T/C und −1154 A/G festgestellt.

Schlussfolgerung

Die vorliegende Metaanalyse ergab bei RA-Patienten signifikant höhere Werte für den zirkulierenden VEGF und eine positive Korrelation zwischen VEGF-Werten und RA-Krankheitsaktivität, aber keinen Zusammenhang zwischen den VEGF-Polymorphismen −2578 A/C, −634 C/G, +936 T/C und −1154 A/G und dem Auftreten einer RA.

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Acknowledgements

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).

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Correspondence to Young Ho Lee MD,PhD.

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Conflict of interest

Y.H. Lee and S.-C. Bae declare that they have no financial or non-financial conflict of interest.

This article does not contain any studies with human participants or animals performed by any of the authors.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Cite this article

Lee, Y.H., Bae, S. Correlation between circulating VEGF levels and disease activity in rheumatoid arthritis: a meta-analysis. Z Rheumatol 77, 240–248 (2018). https://doi.org/10.1007/s00393-016-0229-5

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Keywords

  • VEGF
  • Level
  • Polymorphism
  • Rheumatoid arthritis

Schlüsselwörter

  • VEGF
  • Wert
  • Polymorphismus
  • Rheumatoide Arthritis