F11 is associated with recurrent VTE in women

Maria Bruzelius; Maria Ljungqvist; Matteo Bottai; Annica Bergendal; Rona J. Strawbridge; Margareta Holmström; Angela Silveira; Helle Kieler; Anders Hamsten; Gerd Lärfars; Jacob Odeberg

doi:10.1160/th15-06-0459

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(02): 406-414
DOI: 10.1160/th15-06-0459

Stroke, Systemic or Venous Thromboembolism

Schattauer GmbH

F11 is associated with recurrent VTE in women

A prospective cohort study

Authors

Maria Bruzelius

¹Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden

²Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
Maria Ljungqvist

³Department of Clinical Science and Education, KI Södersjukhuset, Stockholm, Sweden
Matteo Bottai

⁴Unit of Biostatistics, Institute of Environmental Medicine, KI, Stockholm, Sweden
Annica Bergendal

⁵Centre for Pharmacoepidemiology, Department of Medicine Solna, KI, Stockholm, Sweden
Rona J. Strawbridge

²Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
Margareta Holmström

¹Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden

⁶Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Angela Silveira

¹Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden
Helle Kieler

⁵Centre for Pharmacoepidemiology, Department of Medicine Solna, KI, Stockholm, Sweden
Anders Hamsten

²Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
Gerd Lärfars

³Department of Clinical Science and Education, KI Södersjukhuset, Stockholm, Sweden
Jacob Odeberg

¹Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden

²Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden

⁷Department of Proteomics, School of Biotechnology, Science for Life Laboratory, Royal Institute of Technology (KTH), Stockholm, Sweden

Abstract

Summary

Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002–2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95 % CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95 % CI; 1.1–2.6)) and F11 rs2289252 (HR=1.8 (95 % CI; 1.1–3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Epidemiology - polymorphism - single nucleotide - venous thrombosis - women - recurrence

Full Text

References

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Supplementary Material

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