Vitamin K epoxide reductase complex subunit 1 gene promoter polymorphism - a potential genetic basis for survival from thromboembolism in COVID-19

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