prothrombinG20210A

Prothrombin G20210A, also called the F2 G20210A mutation, is a single nucleotide substitution in the prothrombin gene (F2). It involves a guanine to adenine change at nucleotide 20210 (G20210A) and is located in the 3' untranslated region. The mutation is thought to increase prothrombin production, leading to higher plasma prothrombin levels and greater thrombin generation, which can promote clot formation.

Inheritance is autosomal dominant with incomplete penetrance. Heterozygous carriers have an elevated risk of thrombosis, while homozygous individuals are rare and may have a higher risk phenotype.

Prevalence varies by population. Among people of European descent, carrier frequencies are typically around 2–3%, with lower frequencies in other groups. Homozygosity is uncommon.

Clinical significance centers on venous thromboembolism (VTE). The G20210A mutation is a risk factor for VTE, with heterozygotes showing approximately a 2–3 fold increased risk compared with non-carriers; the risk is amplified when other risk factors or thrombophilias are present (for example, Factor V Leiden), or during high-risk situations such as pregnancy, surgery, or prolonged immobilization. The evidence linking the mutation to arterial thrombosis is less consistent.

Diagnosis is made by genetic testing of the F2 gene, typically using PCR-based assays or sequencing to detect the G20210A allele. Heterozygous individuals carry one mutant allele.

Management and counseling emphasize risk modification rather than routine anticoagulation for asymptomatic carriers. Avoidance of estrogen-containing contraception when possible and heightened risk assessment during pregnancy or perioperative periods are common strategies. Individuals with VTE are managed per standard anticoagulation guidelines, with duration influenced by prior events and other risk factors. Family testing may be offered.

See also: Factor V Leiden, inherited thrombophilia, venous thromboembolism.