Association between PAI-1 4G/5G polymorphism and COVID-19 patients with different SARS-CoV-2 variants

• Evren Mogol ^[1] ; Gokce Akan ^[1] ; Ayla Turgay ^[1] ; Gulten Tuncel ^[1] ; Emine Unal Evren ^[2] ; Hakan Evren ^[2] ; Kaya Suer ^[2] ; Tamer Sanlidag ^[1] ; Mahmut Cerkez Ergoren ^{[1] [1]}
  1. [1] Near East University

     Near East University

     Chipre

     
  2. [2] Girne University, Faculty of Medicine, Department of Clinical Microbiology and Infectious Diseases, Kyrenia, Cyprus
• Localización: Academic Journal of Health Sciences: Medicina Balear, ISSN-e 2255-0560, Vol. 39, Nº. 1, 2024, págs. 71-77
• Idioma: inglés
• DOI: 10.3306/AJHS.2024.39.01.71
• Títulos paralelos:
  • Asociación entre el polimorfismo PAI-1 4G/5G y los pacientes COVID-19 con diferentes variantes de SARS-CoV-2
• Enlaces
  • Texto completo (pdf)
• Resumen
  • español

    Introducción: Estudios previos revelaron que el nivel plasmático de PAI-1 aumenta durante la infección por SARS-CoV-2 y, como resultado, aumenta la probabilidad de anomalías de la coagulación durante el curso de la infección. Hasta donde sabemos, no existe ninguna investigación científica que evalúe la asociación entre el polimorfismo 4G/5G del PAI-1 y las variantes preocupantes del SARS-CoV-2.

    Métodos: Se incluyó en el estudio a un total de 408 individuos (204 controles y 204 pacientes). El polimorfismo 4G/5G (rs1799889 A>G) del gen PAI-1 se genotipificó mediante PCR-RFLP. Se registraron los valores Ct de los pacientes COVID-19 para analizar la asociación con el polimorfismo 4G/5G del gen PAI-1 y la carga viral.

    Resultados: Las frecuencias de los genotipos PAI-1 4G/4G, 4G/5G y 5G/5G fueron, 24,5%, 40,2% y 35,3% en los casos frente a 1%, 2% y 97% en los controles, respectivamente. El alelo 4G tiene una distribución significativa entre los casos de la variante Delta y el control, pero no para la variante Omicron. La distribución de las frecuencias de los genotipos PAI-1 4G/5G + 4G/4G y 5G/5G fueron, respectivamente, 79% y 21% en la variante Delta frente a 51% y 49% en la variante Omicron. Los portadores del alelo 4G también presentaron cargas virales más elevadas y valores Ct más bajos.

    Conclusiones: Los valores de Ct en la distribución de frecuencias de genotipos PAI-1 4G/5G + 4G/4G y 5G/5G fueron, 21 y 25 en la variante Delta frente a 26 y 28 en la variante Omicron.

  • English

    Introduction: Previous studies revealed that plasma PAI-1 level increases during SARS-CoV-2 infection and as a result, the probability of coagulation abnormalities during the course of infection increases. To our knowledge, there is no scientific investigation that evaluates the association between PAI-1 4G/5G polymorphism and SARS-CoV-2 variants of concern.

    Methods: Total number of 408 individuals were included in the study (204 control and 204 patients). PAI-1 gene 4G/5G (rs1799889 A>G) polymorphism were genotyped by PCR-RFLP. The Ct values of COVID-19 patients were recorded to analyze the association with PAI-1 4G/5G gene polymorphism and viral load.

    Results: The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were, 24.5%, 40.2% and 35.3% in cases versus 1%, 2% and 97% in controls, respectively. The 4G allele has significant distribution between Delta variant cases and control, but not for the Omicron variant. The distribution of PAI-1 4G/5G + 4G/4G and 5G/5G genotype frequencies were, 79% and 21% in the Delta variant versus 51% and 49% in the Omicron variant, respectively. Carriers of the 4G allele had higher viral loads and lower Ct values as well.

    Conclusion: Ct values in the distribution of PAI-1 4G/5G + 4G/4G and 5G/5G genotype frequencies were, 21 and 25 in the Delta variant versus 26 and 28 in the Omicron variant.

• Referencias bibliográficas
  • Abdullaev A, Fevraleva I, Odilov A, Volkov A, Babichenko I, Sudarikov A. (2021). THROMBOTIC EVENTS AND THE PROFILE OF HEREDITARY THROMBOPHILIA...
  • Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis...
  • Afzali B, Noris M, Lambrecht BN, Kemper C. The state of complement in covid-19. Nature Reviews Immunology 2021; 22(2):77-84. doi.org/10.1038/s41577-021-00665-1
  • Andrianto M, Al-Farabi MJ, Nugraha RA, Marsudi BA, Azmi Y. Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019...
  • Arons MM, Hatfield KM, Reddy SC, Kimball A, James A, Jacobs JR, et al. Presymptomatic SARS-COV-2 infections and transmission in a skilled...
  • Blasi F, Carmeliet P. Upar: A versatile signaling orchestrator. Nature Reviews Molecular Cell Biology 2002; 3(12):932-43. doi.org/10.1038/nrm977
  • Cesari M, Pahor M, Incalzi RA. Review: Plasminogen activator inhibitor-1 (PAI-1): A key factor linking fibrinolysis and age-related subclinical...
  • Fay WP, Garg N, Sunkar M. Vascular functions of the Plasminogen Activation System. Arteriosclerosis, Thrombosis, and Vascular Biology 2007;...
  • Godino C, Scotti A, Maugeri N, Mancini N, Fominskiy E, Margonato A, et al. Antithrombotic therapy in patients with COVID-19? -rationale and...
  • Hammer S, Häberle H, Schlensak C, Bitzer M, Malek NP, Handgretinger R, et al. Severe SARS-COV-2 infection inhibits fibrinolysis leading to...
  • Jak B, Zanirati G, Rodrigues FV, Grahl M, Krimberg F, Pinzetta G, et al. Case report: Placental maternal vascular malperfusion affecting late fetal...
  • Kawakami R, Sakamoto A, Kawai K, Gianatti A, Pellegrini D, Nasr A, et al. Pathological evidence for SARS-COV-2 as a cause of myocarditis. Journal...
  • Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells....
  • Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA. Incidence of venous thromboembolism in hospitalized patients with covid-19....
  • Miri S, Sheikhha MH, Dastgheib SA, Shaker SA, Neamatzadeh H. Association of ace I/D and pai-1 4G/5G polymorphisms with susceptibility to type...
  • Rabaan AA, Tirupathi R, Sule AA, Aldali J, Mutair AA, Alhumaid S, et al. Viral Dynamics and real-time RT-PCR CT values correlation with disease...
  • Romanova ES, Vasilyev VV, Startseva G, Karev V, Rybakova M, Platonov PG. Cause of death based on systematic post-Mortem studies in patients...
  • Sartori MT, Wiman B, Vettore S, Dazzi F, Girolami A, Patrassi GM. 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients...
  • Vatseba B, Virstyuk N. Association between FGB-455 g/a and PAI- 1-675 5g/4g gene polymorphisms and COVID-19 severity. Research and Practice...
  • Waudby-West R, Parcell BJ, Palmer CNA, Bell S, Chalmers JD, Siddiqui MK. The association between SARS-CoV-2 RT-PCR cycle threshold and mortality...
  • Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin- converting enzyme 2 (ACE2) as a SARS-COV-2 receptor: Molecular mechanisms and...
  • Zuo Y, Warnock M, Harbaugh A, Yalavarthi S, Gockman K, Zuo M, Madison JA, Knight JS, Kanthi Y, Lawrence DA. Plasma tissue plasminogen activator...