Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type

CMAJ. 2013 Mar 19;185(5):E229-37. doi: 10.1503/cmaj.121636. Epub 2013 Feb 4.

Abstract

Background: ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population.

Methods: We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction.

Results: The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p<0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0.

Interpretation: ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / genetics*
  • Age Factors
  • Aged
  • Cohort Studies
  • Denmark / epidemiology
  • Factor V / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / physiopathology
  • Polymorphism, Genetic
  • Proportional Hazards Models
  • Prothrombin / genetics*
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Statistics, Nonparametric
  • Survival Rate
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / genetics*
  • Venous Thromboembolism / physiopathology

Substances

  • ABO Blood-Group System
  • factor V Leiden
  • Factor V
  • Prothrombin