[From gene to disease; risk factors for venous thrombosis: factor V Leiden and prothrombin 20210A]

Venous thromboembolic disease is an important clinical entity, in which both acquired and genetic risk factors play a causative role. Genetic factors which increase thrombotic risk consist of rare heterogeneous loss-of-function mutations in coagulation-inhibitory factors, such as antithrombin, protein S and C, and more common, but unique, gain-of-function mutations in coagulation factors V and II, so-called factor V-Leiden and prothrombin 20210A. The genetic defect underlying factor V-Leiden is a guanine (G) to adenine (A) mutation in the factor V gene, causing substitution of arginine at position 506 by glutamine, thereby providing resistance to proteolytic cleavage by activated protein C (APC). In the prothrombin 20210A allele a G to A mutation at nucleotide 20210 in the 3'-untranslated region of the prothrombin gene is associated with increased prothrombin levels. The APC-resistance assay is used to screen for the presence of factor V-Leiden. Both factor V-Leiden and prothrombin 20210A are diagnosed by DNA analysis.