Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      COVID-19/*genetics ; COVID-19/*mortality ; Membrane Glycoproteins/*genetics ; Receptors, Interleukin-1/*genetics; Aged ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/epidemiology ; Cohort Studies ; Factor X/genetics ; Factor X/metabolism ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Male ; Membrane Glycoproteins/metabolism ; Middle Aged ; Netherlands/epidemiology ; Polymorphism, Single Nucleotide/genetics ; Receptors, Interleukin-1/metabolism ; Retrospective Studies ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Severity of Illness Index ; Treatment Outcome
    • Abstract:
      Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19.
      Methods: We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation.
      Results: Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55-75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors.
      Conclusion: This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Membrane Glycoproteins)
      0 (Receptors, Interleukin-1)
      0 (TIRAP protein, human)
      9001-29-0 (Factor X)
      EC 3.4.17.23 (ACE2 protein, human)
      EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
    • Publication Date:
      Date Created: 20220107 Date Completed: 20220118 Latest Revision: 20230917
    • Publication Date:
      20231215
    • Accession Number:
      PMC8740962
    • Accession Number:
      10.1371/journal.pone.0260897
    • Accession Number:
      34995294