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

Carl Arne Løchen Arnesen; Line H Evensen; Kristian Hveem; Maiken E Gabrielsen; John-Bjarne Hansen; Sigrid K Brækkan

doi:10.1016/j.rpth.2024.102343

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

Res Pract Thromb Haemost. 2024 Feb 8;8(2):102343. doi: 10.1016/j.rpth.2024.102343. eCollection 2024 Feb.

Authors

Carl Arne Løchen Arnesen^{1

2}, Line H Evensen¹, Kristian Hveem^{3

4

5}, Maiken E Gabrielsen³, John-Bjarne Hansen^{1

2}, Sigrid K Brækkan^{1

2}

Affiliations

¹ Thrombosis Research Group, Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.
² Thrombosis Research Center, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
³ HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ HUNT Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway.
⁵ Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.

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.

Keywords: epidemiology; risk factors; sex differences; single-nucleotide polymorphism; venous thromboembolism.