The G20210A Mutation of the Prothrombin Gene in Patients with Previous First Episodes of Deep-Vein Thrombosis: Prevalence and Association with Factor V G1691A, Methylenetetrahydrofolate Reductase C677T and Plasma Prothrombin Levels

• Published in: Thrombosis research Vol. 93; no. 1; pp. 1 - 8
• Main Authors: Cattaneo, Marco, Chantarangkul, Veena, Taioli, Emanuela, Santos, José Hermida, Tagliabue, Liliana
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 1999; Elsevier Science
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Child; Deep-vein thrombosis; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Factor V - genetics; Factor V Leiden; Female; Genetic Predisposition to Disease; Genotype; Homocysteine; Humans; Male; Medical sciences; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidoreductases Acting on CH-NH Group Donors - genetics; Prevalence; Prothrombin; Prothrombin - genetics; Prothrombin - metabolism; Risk factor; Risk Factors; Venous Thrombosis - blood; Venous Thrombosis - epidemiology; Venous Thrombosis - genetics; Deep-vein thrombosis; Factor V Leiden; DVT, deep-vein thrombosis; Risk factor; Prothrombin; Methylenetetrahydrofolate reductase; OR, odds ratio; Homocysteine; MTHFR, methylene tetrahydrofolate reductase; Human; Methylenetetrahydrofolate reductase (NADPH); Enzyme; Deep vein thrombosis; Cardiovascular disease; Venous disease; Vascular disease; Oxidoreductases; Mutation; Vein
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(98)00136-4

A common G to A transition at nucleotide 20210 of the prothrombin gene is associated with an increased risk for deep-vein thrombosis (DVT) and high plasma levels of prothrombin. We calculated the prevalences of prothrombin G20210A, factor V G1691A (also associated with high risk for DVT) and homozygous methylenetetrahydrofolate reductase (MTHFR) C677T (associated with increased susceptibility to develop hyperhomocysteinemia) in 118 patients with a first episode of DVT and in 416 healthy controls. 15.9% of the patients and 2.3% of the controls had prothrombin G20210A (odds ratio [OR]: 8.7, 95% C.I.: 3.8–21.4); 21.1% of the patients and 3.2% of the controls had factor V G1691A (OR 7.8, 3.9–17.1); 20.5% of the patients and 21% of the controls had homozygous MTHFR C677T (OR: 1.0, 0.7–1.2). Exclusion of patients with other hereditary risk factors for DVT did not substantially modify the results. Mutant factor V and prothrombin coexisted in three patients but in no control. The concomitant presence of the MTHFR mutation did not increase the thrombotic risk associated with prothrombin G20210A. 63.2% of individuals with prothrombin G20210A had plasma levels of prothrombin in the upper quartile of distribution. After adjustment for age and sex, subjects with prothrombin levels in the upper quartile carried a slightly higher risk for thrombosis than those with lower prothrombin concentrations (OR: 1.9, 1.1–3.2). In conclusion, we found that prothrombin G20210A is relatively common in Italy and is associated with high prothrombin levels and an 8.7-fold increase in the risk for DVT. Such risk is independent of the coexistence of other known inherited risk factors for thrombosis and increases in patients with associated mutant factor V. Whether it is due to the associated increase in plasma prothrombin levels remains to be established.