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

L D Horvei; S K Braekkan; E N Smith; T Solomon; K Hindberg; K A Frazer; F R Rosendaal; J-B Hansen

doi:10.1111/jth.13892

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

J Thromb Haemost. 2018 Jan;16(1):83-89. doi: 10.1111/jth.13892. Epub 2017 Nov 27.

Authors

L D Horvei^{1

2}, S K Braekkan^{1

2}, E N Smith^{1

3}, T Solomon⁴, K Hindberg¹, K A Frazer^{1

3}, F R Rosendaal^{1

5}, J-B Hansen^{1

2}

Affiliations

¹ Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway.
² Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
³ Department of Pediatrics and Rady Children's Hospital, University of California, San Diego, CA, USA.
⁴ Biomedical Sciences Graduate Program, University of California, San Diego, CA, USA.
⁵ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

PMID: 29094466
DOI: 10.1111/jth.13892

Abstract

Essentials Body height and prothrombotic genotypes are associated with risk of venous thromboembolism (VTE). The joint effect of prothrombotic genotypes and tall stature on VTE risk is scarcely investigated. We investigated the joint effect of prothrombotic genotypes and tall stature on VTE risk. Prothrombotic genotypes did not yield excess risk of VTE in subjects with a tall stature.

Summary: 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 (factor V 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 ≥ 178 cm had a two-fold higher VTE risk (HR 2.03; 95% confidence interval [CI] 1.51-2.73) than those with height ≤ 165 cm. 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 ≥ 178 cm had a two-fold (HR 2.08; 95% CI 1.24-3.52) higher VTE risk than subjects ≤ 165 cm 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.

Keywords: SNPs; body height; cohort; risk; venous thromboembolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ABO Blood-Group System / genetics
Aged
Body Height*
Case-Control Studies
Factor IX / genetics
Factor V / genetics
Female
Fibrinogen / genetics
Genetic Predisposition to Disease
Humans
Incidence
Male
Middle Aged
Norway / epidemiology
Phenotype
Polymorphism, Single Nucleotide*
Prospective Studies
Prothrombin / genetics
Risk Assessment
Risk Factors
Venous Thromboembolism / diagnosis
Venous Thromboembolism / epidemiology
Venous Thromboembolism / genetics*
Venous Thromboembolism / physiopathology

Substances

ABO Blood-Group System
FGG protein, human
factor V Leiden
Factor V
Prothrombin
Factor IX
Fibrinogen