Proportion of venous thromboembolism attributed to recognized prothrombotic genotypes in men and women.

ABSTRACT

Background: Data on the proportion of venous thromboembolism (VTE) risk attributed to prothrombotic genotypes in men and women are limited. Objectives: We aimed to estimate the population attributable fraction (PAF) of VTE for recognized, common prothrombotic genotypes in men and women using a population-based case cohort. Methods: Cases with incident VTE (n = 1493) and a randomly sampled subcohort (n = 13,069) were derived from the Tromsø study (1994-2012) and the Trøndelag Health Study (1995-2008) cohorts. DNA samples were genotyped for 17 single-nucleotide polymorphisms (SNPs) previously associated with VTE. PAFs with 95% bias-corrected CIs (based on 10,000 bootstrap samples) were estimated for SNPs significantly associated with VTE, and a 6-SNP cumulative model was constructed for both sexes. Results: In women, the individual PAFs for SNPs included in the cumulative model were 16.9% for ABO (rs8176719), 17.6% for F11 (rs2036914), 15.1% for F11 (rs2289252), 8.7% for FVL (rs6025), 6.0% for FGG (rs2066865), and 0.2% for F2 (rs1799963). The cumulative PAF for this 6-SNP model was 37.8%. In men, the individual PAFs for SNPs included in the cumulative model were 21.3% for ABO, 12.2% for F11 (rs2036914), 10.4% for F11 (rs2289252), 7.5% for FVL, 7.8% for FGG, and 1.1% for F2. This resulted in a cumulative PAF in men of 51.9%. Conclusion: Our findings in a Norwegian population suggest that 52% and 38% of the VTEs can be attributed to known prothrombotic genotypes in men and women, respectively.