Prothrombin A19911G polymorphism and the risk of venous thromboembolism

Summary.  Background: The A > 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 > 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 > G. Plasma prothrombin levels were measured in 342 individuals. Results: Prothrombin 19911 A > 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 > 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 > 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.

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