Joint effects of prothrombotic genotypes and body height on the risk of venous thromboembolism: the Tromsø study

Abstract

Background Studies have reported synergistic effects of prothrombotic single-nucleotide polymorphisms (SNPs) and obesity on the risk of venous thromboembolism (VTE). Tall stature is associated with an increased VTE risk, but the joint effect of prothrombotic genotypes and tall stature on the VTE risk is unknown. Aims To investigate the joint effects of prothrombotic genotypes and tall stature on the VTE risk. Methods Cases with incident VTE (n=676) and a randomly selected age-weighted subcohort (n=1842) were sampled from the Tromsø study (cohort follow-up: 1994-2012). DNA was genotyped for rs6025 (factorV Leiden), rs1799963 (FII), rs8176719 (ABO blood group), rs2066865 (fibrinogen-γ), and rs2036914 (FIX). Age-adjusted and sex-adjusted hazard ratios (HRs) of VTE were calculated by categories of risk alleles (de Haan 5-SNP score: 0-1, 2-3, and ≥4) and body height (<40th, 40th-80th and >80th percentiles). Results The VTE risk increased by increasing category of body height, and subjects with height ≥178cm had a two-fold higher VTE risk (HR2.03; 95% confidence interval [CI]1.51-2.73) than those with height ≤165cm. The VTE risk also increased across categories of risk alleles. However, the combination of a tall stature and risk alleles, either individual SNPs or risk score, did not result in an excess VTE risk. Subjects with four or more risk alleles and height ≥178cm had a two-fold (HR2.08; 95%CI1.24-3.52) higher VTE risk than subjects ≤165cm with no risk allele or one risk allele. Conclusions In contrast to obesity, the presence of prothrombotic genotypes did not result in an excess VTE risk in subjects with a tall stature.