Impact of prothrombotic genotypes on the association between family history of myocardial infarction and venous thromboembolism

• Published in: Journal of Thrombosis and Haemostasis
• Main Authors: Småbrekke, Birgit, Balteskard Rinde, Ludvig, Evensen, Line Holtet, Morelli, Vania Maris, Hveem, Kristian, Gabrielsen, Maiken Elvestad, Njølstad, Inger, Mathiesen, Ellisiv B., Rosendaal, Frits Richard, Brækkan, Sigrid Kufaas, Hansen, John-Bjarne
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2019
• Subjects: VDP::Medical disciplines: 700; VDP::Medisinske Fag: 700; Evensen; Tromsø
• Online Access: https://hdl.handle.net/10037/17265; https://doi.org/10.1111/jth.14493

This is the peer reviewed version of the following article: Småbrekke, B., Rinde, L., Evensen, L., Morelli, V., Hveem, K., Gabrielsen, M., . Hansen, J. (2019). Impact of prothrombotic genotypes on the association between family history of myocardial infarction and venous thromboembolism. Journal of Thrombosis and Haemostasis, 17 (8), 1363-1371., which has been published in final form at https://doi.org/10.1111/jth.14493 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Background : Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). Objectives : To investigate the effect of prothrombotic genotypes on the association between FHMI and VTE in a case‐cohort recruited from a general population. Methods : Cases with a first VTE ( n = 1493) and a subcohort ( n = 13 072) were sampled from the Tromsø study (1994‐2012) and the Nord‐Trøndelag health (HUNT) study (1995‐2008). The DNA samples were genotyped for rs8176719 ( ABO ), rs6025 ( F5 ), rs1799963 ( F2 ), rs2066865 ( FGG ), and rs2036914 ( F11 ). Participants with missing information on risk alleles ( n = 175), FHMI ( n = 2769), and BMI ( n = 52) were excluded. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for VTE. To explore the role of prothrombotic genotypes for the association between FHMI and VTE, we (a) included the genotypes in the multivariable‐adjusted models and (b) assessed the joint effects between FHMI and genotypes on VTE risk. Results : The FHMI was associated with a 1.3‐fold increased risk of VTE (HR 1.32, 95% CI 1.16‐1.50) and 1.5‐fold increased risk of unprovoked VTE (HR 1.47, 95% CI 1.22‐1.78). The risk of VTE by FHMI did not alter after adjustment for the five genotypes. The combination of FHMI and the different prothrombotic genotypes did not result in an excess VTE risk (i.e. no biological interaction). Conclusions : Our findings suggest that the risk of VTE by FHMI is not explained by rs8176719 ( ABO ), rs6025 ( F5 ), rs1799963 ( F2 ), rs2066865 ( FGG ), and rs2036914 ( F11 ). The combination of FHMI with prothrombotic genotypes had an additive effect on VTE risk.