[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.
Reitsma
P H
PH
European School for Science Education, Eikenheuveldreef 16, 5263 EM Vught.
van de Stolpe
A
A
D020016:Activated Protein C Resistance / Q000235:genetics*; D000483:Alleles; D019774:Blood Coagulation Factor Inhibitors / Q000235:genetics; D003937:Diagnosis, Differential; D005165:Factor V / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011516:Prothrombin / Q000235:genetics*; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
D019774:Blood Coagulation Factor Inhibitors; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin