Are ABO Gene Alleles Responsible for Cardiovascular Diseases and Venous Thromboembolism and Do They Play a Role in COVID?

Abstract

Cardiovascular diseases (CVD) including coronary heart disease and stroke are leading causes of death and disability globally. Studies of the association between ABO blood groups and CVD have consistently demonstrated an increased risk of coronary heart disease, myocardial infarction, cerebral ischaemic stroke, peripheral arterial disease and venous thromboembolism (VTE) including deep vein thrombosis and pulmonary thromboembolism in patients who possess a non-O blood group type. The most likely mechanism is thought to be the increase in von Willebrand Factor (vWF) and factor VIII levels seen in patients with a non-O blood group. Other postulated mechanisms include elevations in circulating inflammatory markers such as endothelial cell and platelet adhesion molecules in subjects with a non-O blood group. More recently, it has also been recognised that individuals with a non-O blood group type carry a higher risk of SARS-C0V-2 infection and COVID-19 related complications. The increased levels in vWF and factor VIII amongst individuals with a non-O blood group who have contracted SARS-CoV-2 infection may result in an additive thrombophilic effect to that caused by the SARS-CoV-2 virus. Another postulated mechanism is that individuals with an O-blood group are protected by anti-A and B antibodies which possibly inhibit the binding of the SARS-CoV-2 spike protein to lung epithelium angiotensin converting enzyme-2 receptors. There are over 35 minor blood groups on red blood cells, some of which such as Kidd, Lewis and Duffy have been associated with CVD either alone or in combination with a non-O blood group allele(s). However, their role in SARS-CoV-2 infection and mechanism of action for an association with CVD remain unknown. This review explores the relationship between ABO and minor blood groups with CVD and VTE, with a focus on potential mechanisms underlying this relationship and the potential role of ABO blood group types in COVID.