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Association between plasminogen activator inhibitor‑1 (PAI-1) 4G/5G polymorphism and circulating PAI-1 level in systemic lupus erythematosus and rheumatoid arthritis

A meta-analysis

Zusammenhang zwischen PAI-1(Plasminogenaktivator-Inhibitor)-4G/5G-Polymorphismus und zirkulierendem PAI-1 bei systemischem Lupus erythematosus und rheumatoider Arthritis

Eine Metaanalyse

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Abstract

Objective

This study systemically reviewed the evidence regarding the association between plasminogen activator inhibitor‑1 (PAI‑1) 4G/5G polymorphism and susceptibility to systemic lupus erythematous (SLE)/lupus nephritis (LN) and rheumatoid arthritis (RA) and the relationship between circulating PAI‑1 levels and SLE/LN and RA.

Methods

We conducted a meta-analysis on the association between the PAI‑1 4G/5G polymorphism and SLE/LN or RA risk and serum/plasma PAI‑1 levels in patients with SLE/LN and RA and healthy controls.

Results

Nine articles including 657 patients with SLE and 668 controls and 567 patients with RA and 772 controls were included. No association was revealed between SLE and PAI‑1 4G allele in all study subjects (odds ratio [OR] = 0.944, 95% confidence interval [CI] = 0.808–1.102, p = 0.463). Ethnicity-based stratification showed no association between the PAI‑1 4G allele and SLE among Europeans and Asians. No association was detected between LN and RA and the PAI‑1 4G allele (OR = 0.886, 95% CI = 0.713–1.102, p = 0.278; OR = 0.8736, 95% CI = 0.747–1.020, p = 0.088, respectively) or between SLE/LN and RA and the PAI‑1 4G/5G polymorphism using the recessive and dominant models and homozygote contrast. The circulating PAI‑1 level was significantly higher in the SLE group than in the control group (standardized mean difference [SMD] = 0.337, 95% CI = 0.057–0.619, p = 0.019). However, serum/plasma PAI‑1 level showed no significant difference between RA and control group (SMD = 0.333, 95% CI = −0.6989–1.35, p = 0.527).

Conclusions

There was no association between the PAI‑1 4G/5G polymorphism and SLE/LN and RA development and significantly higher levels of circulating PAI‑1 were observed in patients with SLE but not in those with RA.

Zusammenfassung

Zielsetzung

In der Studie wurde systematisch die Evidenz für einen Zusammenhang zwischen dem PAI‑1(Plasminogenaktivator-Inhibitor)-4G/5G-Polymorphismus und der Suszeptibilität für systemischen Lupus erythematous (SLE)/Lupusnephritis (LN) bzw. rheumatoide Arthritis (RA) und für eine Beziehung zwischen der Höhe an zirkulierendem PAI‑1 und SLE/LN bzw. RA untersucht.

Methoden

Wir führten eine Metaanalyse durch zum Zusammenhang zwischen PAI-1-4G/5G-Polymorphismus und SLE/LN- bzw. RA-Risiko sowie zwischen Serum/Plasma-PAI-1-Level bei Patienten mit SLE/LN und RA sowie gesunden Kontrollen.

Ergebnisse

Neun Publikationen (657 SLE-Patienten, 668 Kontrollen; 567 RA-Patienten, 772 Kontrollen) wurden in die Metaanalyse aufgenommen. Es zeigte sich kein Zusammenhang zwischen SLE und PAI-1-4G-Allel bei allen Teilnehmenden (Odds Ratio [OR] 0,944, 95 %-Konfidenzintervall [KI] 0,808–1,102; p = 0,463). Eine Stratifizierung nach Ethnizität zeigte keinen Zusammenhang zwischen dem PAI-1-4G-Allel und SLE bei Europäern und Asiaten, ebenso bestand keiner zwischen LN bzw. RA und dem PAI-1-4G-Allel (OR 0,886, 95 %–KI 0,713‑1,102, p = 0,278; OR 0,8736, 95 %-KI 0,747‑1,020, p = 0,088) bzw. zwischen SLE/LN bzw. RA und dem PAI-1-4G/5G-Polymorphismus unter Verwendung der rezessiven und dominanten Modelle und des „homozygote contrast“. Der zirkulierende PAI-1-Wert war in der SLE-Gruppe signifikant höher als in der Kontrollgruppe (standardisierte mittlere Differenz [SMD] 0,337, 95 %-KI 0,057–0,619, p = 0,019), doch der PAI-1-Spiegel im Serum/Plasma wies keinen signifikanten Unterschied auf zwischen RA- und Kontrollgruppe (SMD 0,333, 95 %-KI -0,6989–1,35, p = 0,527).

Schlussfolgerungen

Es gab keinen Zusammenhang zwischen dem PAI-1-4G/5G-Polymorphismus und SLE/LN- bzw. RA-Entwicklung. Signifikant erhöhte Level an zirkulierendem PAI‑1 wurden bei SLE-, nicht aber bei RA-Patienten beobachtet.

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Acknowledgements

This study was supported in part by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2017M3A9B4050335), Republic of Korea.

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Authors and Affiliations

  1. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (Republic of)

    S.-C. Bae

  2. Department of Rheumatology, Korea University College of Medicine, Seoul, Korea (Republic of)

    Y. H. Lee MD, PhD

  3. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of)

    Y. H. Lee MD, PhD

Authors
  1. S.-C. Bae
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Correspondence to Y. H. Lee MD, PhD.

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S.-C. Bae and Y. H. Lee declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Bae, SC., Lee, Y.H. Association between plasminogen activator inhibitor‑1 (PAI-1) 4G/5G polymorphism and circulating PAI-1 level in systemic lupus erythematosus and rheumatoid arthritis. Z Rheumatol 79, 312–318 (2020). https://doi.org/10.1007/s00393-019-00689-y

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