|Classification and external resources|
Prothrombin G20210A (also the prothrombin 20210 mutation, the factor II mutation, or the prothrombin mutation) is a genetic variant that approximately doubles or triples the risk of forming blood clots in the veins. The variant is commonly associated with the disease venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism. Most carriers, though, never develop VTE in their lifetime.
Prothrombin G20210A was identified in the 1990s, is almost exclusively present in Caucasians, and is estimated to have originated in that population slightly over 20,000 years ago. About 2 to 3% of Caucasians carry the variant, and it confers a 2- to 3-fold higher risk of VTE. Deficiencies in the anticoagulants Protein C and Protein S give a higher risk (5- to 10-fold). Behind non-O blood type and factor V Leiden, prothrombin G20210A is one of the most common genetic risk factors for VTE.
The polymorphism is located in a noncoding region of the prothrombin gene (3' untranslated region nucleotide 20210[a]), replacing guanine with adenine. The position is at or near where the pre-mRNA will have the poly-A tail attached. The variant causes elevated plasma prothrombin levels (hyperprothrombinemia), possibly due to increased pre-mRNA stability. Prothrombin is the precursor to thrombin, which plays a key role in causing blood to clot (blood coagulation). G20210A can thus contribute to a state of hypercoagulability, but not particularly with arterial thrombosis. A 2006 meta-analysis showed only a 1.3-fold increased risk for coronary disease.
Heterozygous carriers who take oral contraceptives are at a 15-fold increased risk of VTE, while carriers also heterozygous with factor V Leiden have an approximate 20-fold higher risk. In a recommendation statement on VTE, genetic testing for G20210A in adults that developed unprovoked VTE[b] was disadvised, as was testing in asymptomatic family members related to G20210A carriers who developed VTE. In those who develop VTE, the results of thrombophilia tests (wherein the variant can be detected) rarely play a role in the length of treatment.
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