Prothrombin A19911G polymorphism and the risk of venous thromboembolism

Background: The A &rt; G polymorphism at position 19911 of the prothrombin gene is associated with increased plasma prothrombin levels but its role as a risk factor for venous thromboembolism (VTE) is not established. Objective: To investigate the role of prothrombin 19911 A &rt; G polymorphism in the risk of VTE in patients with heterozygous prothrombin 20210GA or factor (F) V Leiden and in those without thrombophilia. Patients and methods: Case-control study of 793 patients with prothrombin 20210 GA (n= 167) or FV Leiden (n= 198), and without thrombophilia (n= 428), and of 795 healthy individuals with the corresponding coagulation profile, investigated for the presence of prothrombin 19911 A &rt; G. Plasma prothrombin levels were measured in 342 individuals. Results: Prothrombin 19911 A &rt; G did not increase the risk of VTE in carriers of prothrombin 20210 GA [odds ratio (OR) 1.2, 95% CI (95% CI) 0.8-1.8] but significantly increased the risk in carriers of FV Leiden (OR 2.1, 95% CI 1.3-3.4) and in patients without thrombophilia (OR 1.5, 95% CI 1.0-2.2). Higher plasma prothrombin levels in carriers of prothrombin 19911 A &rt; G polymorphism than in non-carriers were found among individuals without thrombophilia (P= 0.05) and with FV Leiden (P= 0.07), but not in carriers of prothrombin 20210 GA (P= 0.2). Conclusions: Prothrombin 19911 A &rt; G polymorphism was independently associated with a 1.5-fold increased risk of VTE and increased 2-fold the risk of VTE associated with FV Leiden, both increases statistically significant. No effect was observed in carriers of prothrombin 20210 GA, perhaps because this polymorphism has a stronger influence on plasma prothrombin levels than the prothrombin 19911 polymorphism. (copyright) 2006 International Society on Thrombosis and Haemostasis.