Molecular Genetics of Venous Thromboembolism

Venous thrombosis is often familial, but until recently well-defined genetic defects were only found in a minority of patients. The situation changed with the discovery of inherited resistance to activated protein C (APC) as a novel mechanism for familial thrombophilia. It is caused by a single point mutation in the factor V gene, which predicts replacement of Arg506 in the APC-cleavage site with a Gln. APC resistance is found in a majority of patients with familial thrombosis as well as in 3-7% of the general population. It afflicts affected individuals with a life-long increased risk of thrombosis. The factor V gene mutation is the most prevalent single gene defect associated with thromboembolic disease so far described.