Vitamin K epoxide reductase complex subunit 1 gene promoter polymorphism – a potential genetic basis for survival from thromboembolism in COVID-19
Mirsada Causevic1, Amina Sahbaz1, Nedim Galijasevic1, Lamija Sikalo1 , Slobodan Jankovic2 , Edin Begic1,3
1 1Sarajevo Medical School, University Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina
2 Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
3 Department of Cardiology, General Hospital “Prim.dr.Abdulah Nakas”, Sarajevo, Bosnia and Herzegovina
Corresponding Author: Dr Mirsada Causevic, PhD, Sarajevo Medical School, University Sarajevo School of Science
and Technology, Hrasnicka cesta 3a, Sarajevo 71000, Bosnia and Herzegovina; E-mail: mirsada.causevic@ssst.edu.ba; Phone: +387 33 975-001; ORCID ID: 0000-0002-6099-6415.
Cite this article: Causevic M, Sahbaz A, Galijasevic N, Sikalo L, Jankovic S, Begic E. Vitamin K epoxide reductase
complex subunit 1 gene promoter polymorphism – a potential genetic basis for survival from thromboembolism
in COVID-19. Sar Med J. 2024; 1(2): Online ahead of print. 
10.70119/0014-24
Pages: 56-62 / Published online: 18 November 2024
Original submission: 15 October 2024; Revised submission: 07 November 2024; Accepted: 11 November 2024
Abstract
Introduction. The coronavirus induced disease 2019 (COVID-19), caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), which was identified in patients in China in 2019, was pronounced a pandemic in March 2020. It resulted in more than 7 million deaths worldwide. As hypercoagulation emerged as its key pathological hallmark, the objective of this study was to investigate if a polymorphism within the VKORC1 gene, which plays a role in the vitamin K-dependent blood coagulation pathway, contributed to the survival from thrombosis in individuals who developed some form of it during their COVID-19.
Methods. This was an observational, case-control study. Characterization of the VKORC1 -1639G>A (rs9923231) polymorphism-associated genotypes was carried out in cases (N=16), volunteers who developed some form of thromboembolism during COVID-19, but who survived from it, and controls (N=32), volunteers who did not develop any form of thromboembolism during COVID-19, by using polymerase chain reaction restriction fragment length polymorphism method, followed by Sanger sequencing of the VKORC1 gene promoter-specific, polymerase
chain reaction-amplified products.
Results. Our preliminary data indicate that the variant or A allele, which is associated with intermediate or low blood coagulability, is more frequently present within the VKORC1 gene of individuals who developed some form of thromboembolism during their COVID-19, but who survived from it, than the wild-type or G allele, which is associated with standard or high blood coagulability.
Conclusion. These results warrant further studies into the role of the VKORC1 promoter-associated polymorphism in the COVID-19-associated coagulopathy, as the specific VKORC1 genotypes could become genetic biomarkers for prediction of a thrombotic state during COVID-19, and possibly, other thrombosis-associated diseases and disorders.
Keywords: COVID-19, Hypercoagulability, Thrombosis, Venous thromboembolism, Vitamin K epoxide reductase.
