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: Smabrekke, B., Rinde, L.B., Evensen, L.H., Morelli, V.M., Hveem, K., Gabrielsen, M.E., Njolstad, I., Mathiesen, E.B., Rosendaal, F.R., Braekkan, S.K., Hansen, J.B.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2019
• Subjects: genotype; myocardial infarction; prospective studies; risk factors; venous thromboembolism; Tromso
• Online Access: https://hdl.handle.net/1887/122523; https://doi.org/10.1111/jth.14493

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 Tromso study (1994-2012) and the Nord-Trondelag 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. Clinical epidemiology