Background: A mutation in the prothrombin gene (G-->A20210) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis.
Objective: To determine whether the prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis.
Design: Case-control study.
Setting: Two thrombosis centers in southern Italy.
Patients: 281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls.
Measurements: Medical history was collected on standardized questionnaires. The presence of prothrombin G-->A2020 and factor V Leiden mutations was determined by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined by tests of function.
Results: In 150 controls, increased prothrombin activity (P < 0.001) was associated with the prothrombin A20210 allele. This allele was more frequent in patients than in controls (8.01% compared with 2.29%; P < 0.001) and was associated with an increased risk for thrombosis (odds ratio, 3.88 [95% CI, 2.23 to 6.74]). The increased prevalence of this allele was independent of the presence of the factor V Leiden mutation. After adjustment for sex, age, arterial thrombosis, and factor V Leiden mutation, the risk was still significantly elevated (odds ratio, 3.13 [CI, 1.89 to 5.21]). Moreover, the overall prevalence of inherited coagulation abnormalities was significantly higher in patients with thrombosis of the lower extremities than in patients with thrombosis of the upper extremities (odds ratio, 3.77 [CI, 1.10 to 12.93]). Fourteen patients carried both the prothrombin G-->A20210 and factor V Leiden mutations.
Conclusions: The prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis, particularly in patients with a history of thrombosis of the lower extremities.