Increased Risk for Venous Thrombosis in Carriers of the Prothrombin G→A^20210 Gene Variant

Abstract

A mutation in the prothrombin gene (G→A²⁰²¹⁰) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis. To determine whether the prothrombin A²⁰²¹⁰ allele is independently associated with the occurrence of venous thrombosis. Case-control study. Two thrombosis centers in southern Italy. 281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls. Medical history was collected on standardized questionnaires. The presence of prothrombin G→A²⁰²¹⁰ 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. 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. 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.