Prothrombin gene mutation

Prothrombin G20210A is a genetic condition that increases the risk of blood clots including deep vein thrombosis and pulmonary embolism. One copy of the mutation increases the risk of a blood clot from 1 in 1,000 per year to 2.5 in 1,000. Two copies increases the risk to up to 20 in 1,000 per year. Most people never develop a blood clot in their lifetimes. Prothrombin G20210A is a genetic condition that increases the risk of blood clots including deep vein thrombosis and pulmonary embolism. One copy of the mutation increases the risk of a blood clot from 1 in 1,000 per year to 2.5 in 1,000. Two copies increases the risk to up to 20 in 1,000 per year. Most people never develop a blood clot in their lifetimes. It is due to a specific gene mutation in which a guanine (G) is changed to an adenine (A) at position 20210 of the DNA of the prothrombin gene. Other blood clotting pathway mutations that increase the risk of clots include factor V Leiden. Prothrombin G20210A was identified in the 1990s. About 2% of Caucasians carry the variant, while it is less common in other populations. It is estimated to have originated in Caucasians about 20,000 years ago. 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. Deficiencies in the anticoagulants Protein C and Protein S further increase the risk five- to tenfold. Behind non-O blood type and factor V Leiden, prothrombin G20210A is one of the most common genetic risk factors for VTE. Increased production of prothrombin heightens the risk of blood clotting. Moreover, individuals who carry the mutation can pass it on to their offspring. The mutation increases the risk of developing deep vein thrombosis (DVT), which can damage veins throughout the body, causing pain and swelling and sometimes leading to disability.Most individuals do not require treatment but do need to be cautious during periods when the possibility of blood clotting are increased; for example, during pregnancy, after surgery, or during long flights. Occasionally, blood-thinning medication may be indicated to reduce the risk of clotting. Heterozygous carriers who take combined birth control pills 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 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. The polymorphism is located in a noncoding region of the prothrombin gene (3' untranslated region nucleotide 20210), replacing guanine with adenine. The position is at or near where the pre-mRNA will have the poly-A tail attached.