Prothrombin G20210A

Prothrombin G20210A is a genetic variant (a single-nucleotide polymorphism) that predisposes humans towards forming blood clots in the veins (venous thrombosis or VT). It is one of the most common genetic risk factors, along with factor V Leiden, for developing VT. A classical VT is deep vein thrombosis (DVT), which can break off (embolize), and become a life-threatening pulmonary embolism (PE). The two conditions of DVT and PE encompass the term venous thromboembolism (VTE).

The polymorphism is located in a noncoding region of the prothrombin gene (3' untranslated region nucleotide 20210), replacing guanine with adenine. Specifically, position 20210 refers to the nucleotide on the sense strand downstream from the DNA that codes for the start codon (ATG, positions 1 to 3). 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). G20120A 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.

Prothrombin G20210A is almost exclusively present in Caucasians, and it is estimated to have originated in that population slightly over 20,000 years ago. It confers an about 2- to 3-fold higher risk of thrombosis. About 2 to 3% of Caucasians carry the variant, and it is present in about 6% of all individuals that have VT. The increased risk can be viewed as moderate, with deficiencies in anticoagulants (Protein C and Protein S) giving a higher risk (5- to 10-fold), but carriers who take oral contraceptives are at a 15-fold increased risk of VT. Carriers doubly heterozygous with factor V Leiden have a 20-fold higher risk of VT. Overall, most carriers of the variant do not develop thrombosis. In a recommendation statement on VTE, genetic testing for G20210A in adults that developed idiopathic (risk factor-less) VTE was disadvised, as was testing in asymptomatic family members related to G20210A carriers who developed VTE.

The variant was discovered in the 1990s, as was factor V Leiden.