Role of prothrombin 19911 A>G polymorphism, blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

J Thromb Thrombolysis. 2021 Feb;51(2):494-501. doi: 10.1007/s11239-020-02169-6.

Abstract

The role of the A>G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism [VTE] is still unclear. To evaluate the presence of the F2 polymorphism in VTE patients compared to healthy blood donors and to adjust the results for common inherited thrombophilias [IT], age at onset and blood group [BG], and to calculate the risk of VTE recurrence. We investigated 1012 Caucasian patients with a diagnosis of VTE for the presence of the F2 rs3136516 polymorphism and compared these with 902 healthy blood donors. Odds ratios [OR] together with their 95% confidence intervals were calculated adjusted for F5 at rs6025, F2 at rs1799963, blood group, age and gender. In addition, we evaluated the risk of recurrent VTE during patient follow-up calculating hazard ratios [HR] together with their 95% CI. Compared with the AA wildtype, the F2 GG and AG genotypes (rs3136516) were associated with VTE (OR 1.48 and 1.45). The OR in F5 carriers compared to controls was 5.68 and 2.38 in patients with F2 (rs1799963). BG "non-O" was significantly more often diagnosed in patients compared to BG "O" (OR 2.74). VTE recurrence more often occurred in males (HR 2.3) and in carriers with combined thrombophilia (HR 2.11). Noteworthy, the rs3136516 polymorphism alone was not associated significantly with recurrence. In Caucasian patients with VTE the F2 GG/GA genotypes (rs3136516) were moderate risk factors for VTE. Recurrence was associated with male gender and combined thrombophilia.

Keywords: Male gender; Prothrombin 19911 A>G polymorphism; Recurrence; Thrombosis.

MeSH terms

  • Adult
  • Blood Group Antigens* / blood
  • Female
  • Genetic Predisposition to Disease
  • Germany / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prothrombin / genetics*
  • Risk Factors
  • Sex Factors
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / genetics*
  • Young Adult

Substances

  • Blood Group Antigens
  • Prothrombin