Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism

Tobias Frischmuth; Kristian Hindberg; Maiken E. Gabrielsen; Ben Brumpton; Kristian Hveem; Sigrid K. Brækkan; John-Bjarne Hansen; Vânia M. Morelli

doi:10.1055/a-1497-9777

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2022; 122(02): 267-276
DOI: 10.1055/a-1497-9777

Stroke, Systemic or Venous Thromboembolism

Joint Effect of Multiple Prothrombotic Genotypes and Obesity on the Risk of Incident Venous Thromboembolism

Authors

Tobias Frischmuth

¹Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway
Kristian Hindberg

¹Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway
Maiken E. Gabrielsen

²Department of Public Health, K. G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway
Ben Brumpton

²Department of Public Health, K. G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway
Kristian Hveem

²Department of Public Health, K. G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway

³Department of Public Health, HUNT Research Center, Norwegian University of Science and Technology, Levanger, Norway
Sigrid K. Brækkan

¹Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway

⁴Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
John-Bjarne Hansen

¹Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway

⁴Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Vânia M. Morelli

¹Department of Clinical Medicine, K.G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT - The Arctic University of Norway, Tromsø, Norway

Abstract

Background The impact of the combination of obesity and multiple prothrombotic genotypes on venous thromboembolism (VTE) risk remains unclear.

Objective To investigate the joint effect of obesity and a genetic risk score (GRS) composed of established prothrombotic single nucleotide polymorphisms (SNPs) on VTE risk using a population-based case–cohort.

Methods Cases with incident VTE (n = 1,470) and a subcohort (n = 12,826) were derived from the Tromsø Study (1994–2012) and the Trøndelag Health Study (HUNT) (1995–2008). Participants were genotyped for ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865), and F11 (rs2036914) SNPs. Age- and sex-adjusted hazard ratios (HRs) were estimated according to body mass index (BMI) categories and number of risk alleles for individual SNPs and the GRS (0–1, 2, 3, ≥4 alleles).

Results The combination of obesity (BMI ≥ 30kg/m²) and risk alleles, either as individual SNPs or as a GRS, had an additive effect on VTE risk (i.e., no biological interaction). Obese subjects who were carriers of ≥4 risk alleles had a 2.85-fold (95% confidence interval [CI]: 2.05–3.96) increased risk of overall VTE compared with those with BMI <25 kg/m² and 0 to 1 risk allele. However, in subgroups, the combination of obesity and ≥4 risk alleles was more pronounced for deep vein thrombosis (DVT) (HR: 3.20; 95% CI: 2.09–4.90) and unprovoked VTE (HR: 3.82; 95% CI: 2.25–6.47), suggesting a supra-additive effect.

Conclusion Our findings indicate that the combination of obesity and GRS has an additive effect on the risk of overall VTE. However, it may have a supra-additive effect on the risk of DVT and unprovoked VTE.

Keywords

deep vein thrombosis - interaction - obesity - single nucleotide polymorphisms - venous thromboembolism

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Referenzen

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