Evidence map›Paper›PMID 39281671›Full record

ArticleFrontiers in immunology2024

The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction.

Tetiana Yatsenko, Ricardo Rios, Tatiane Nogueira, Yousef Salama, Satoshi Takahashi, Eisuke Adachi, Yoko Tabe, Nobutaka Hattori, Taro Osada, Toshio Naito and 3 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Tetiana YatsenkoDepartment of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Ricardo RiosInstitute of Computing, Federal University of Bahia, Salvador, Bahia, Brazil.
Tatiane NogueiraInstitute of Computing, Federal University of Bahia, Salvador, Bahia, Brazil.
Yousef SalamaAn-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Satoshi TakahashiDivision of Clinical Precision Research Platform, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Eisuke AdachiDepartment of Infectious Diseases and Applied Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Yoko TabeDepartment of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Nobutaka HattoriCenter for Genome and Regenerative Medicine, Juntendo University, Graduate School of Medicine, Tokyo, Japan.
Taro OsadaDepartment of Gastroenterology, Juntendo University, Urayasu Hospital, Urayasu-shi, Japan.
Toshio NaitoDepartment of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Kazuhisa TakahashiDepartment of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Koichi HattoriCenter for Genome and Regenerative Medicine, Juntendo University, Graduate School of Medicine, Tokyo, Japan.
Beate HeissigDepartment of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Plasminogen activator inhibitor-1 (PAI-1) is linked to thrombosis and endothelial dysfunction in severe COVID-19. The +43 G>A PAI-1 and 4G/5G promoter polymorphism can influence PAI-1 expression. The 4G5G PAI-1 promoter gene polymorphism constitutes the 4G4G, 4G5G, and 5G5G genotypes. However, the impact of PAI-1 polymorphisms on disease severity or endothelial dysfunction remains unclear. Methods: Clinical data, sera, and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients were studied. Results: Comorbidities and clinical biomarkers did not correlate with genotypes in either polymorphism. However, differences between fibrinolytic factors and interleukin-1β (IL-1β) were identified in genotypes of the 4G/5G but not the 43 G>A PAI polymorphism. Patients with the 4G4G genotype of the 4G/5G polymorphism showed high circulating PAI-1, mainly complexed with plasminogen activators, and low IL-1β and plasmin levels, indicating suppressed fibrinolysis. NFκB was upregulated in PBMCs of COVID-19 patients with the 4G4G genotype. Discussion: Mechanistically, IL-1β enhanced PAI-1 expression in 4G4G endothelial cells, preventing the generation of plasmin and cleavage products like angiostatin, soluble uPAR, and VCAM1. We identified inflammation-induced endothelial dysfunction coupled with fibrinolytic system overactivation as a risk factor for patients with the 5G5G genotype.

Indexed as

COVID-19Plasminogen Activator Inhibitor 1Promoter Regions, GeneticSARS-CoV-2AdultAgedFemaleGenotypeHumansInterleukin-1betaLeukocytes, MononuclearMaleMiddle AgedPolymorphism, Single NucleotideSeverity of Illness IndexInterleukin-1betaPlasminogen Activator Inhibitor 1SERPINE1 protein, humanCOVID-19endothelial cellsinflammationPAI-1 4G/5G promoter polymorphism (rs1799889)PAI-1 polymorphism +43G>A (rs6092)plasmin; interleukin-1-βplasminogen activator inhibitor-1

Identifiers

PMID39281671
PMCPMC11392769

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.