Homozygosity for the C46T polymorphism of the F12 gene is a risk factor for venous thrombosis during the first pregnancy

Background: A first thromboembolic event during pregnancy and puerperium is predisposed to by polymorphisms G1691A in the factor V gene (F5) (F5G1691A) and G20210A in the prothrombin gene (F2) (F2G20210A). Objectives: To study another potentially frequent thrombogenic polymorphism, C46T in the factor XII gene (F12) (F12C46T). Patients and methods: The 32 463 previously asymptomatic women included in the NOHA First cohort in their first pregnancy were investigated for these three polymorphisms. No other constitutional or acquired thrombophilic risk factor was studied. Results: The overall incidence - absolute risk - of venous thromboembolic events (VTE) was 127 per 100 000 woman-years and was reduced to 22 per 100 000 women-years in women negative for the three polymorphisms (P < 0.0001). Homozygosity for F12C46T was associated with a significant relative risk (RR) of VTE [RR: 5.99, 95% confidence interval (95% CI): 2.1-17.3, P = 0.001], as was heterozygosity for F5G1691A (RR: 18.7, 95% CI: 8.3-42, P < 0.0001), heterozygosity for F2G20210A (RR: 14.3, 95% CI: 6.2-33.2, P < 0.0001), maternal age (RR: 1.18, 95% CI: 1.07-1.29, P = 0.0006), maternal body mass index (RR: 1.31, 95% CI: 1.11-1.55, P = 0.002), conceptus weight (percentiles adjusted for term of delivery; RR: 0.90, 95% CI: 0.88-0.93, P < 0.0001) and pre-eclampsia (RR: 3.03, 95% CI: 1.06-8.69, P = 0.039). Conclusions: Homozygosity for the C46T polymorphism of the F12 gene is associated with venous thrombosis during the first pregnancy/puerperium in previously asymptomatic women.