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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
Maria Bruzelius
1   Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden
2   Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
,
Maria Ljungqvist
3   Department of Clinical Science and Education, KI Södersjukhuset, Stockholm, Sweden
,
Matteo Bottai
4   Unit of Biostatistics, Institute of Environmental Medicine, KI, Stockholm, Sweden
,
Annica Bergendal
5   Centre for Pharmacoepidemiology, Department of Medicine Solna, KI, Stockholm, Sweden
,
Rona J. Strawbridge
2   Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
,
Margareta Holmström
1   Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden
6   Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
,
Angela Silveira
1   Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden
,
Helle Kieler
5   Centre for Pharmacoepidemiology, Department of Medicine Solna, KI, Stockholm, Sweden
,
Anders Hamsten
2   Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
,
Gerd Lärfars
3   Department of Clinical Science and Education, KI Södersjukhuset, Stockholm, Sweden
,
Jacob Odeberg
1   Coagulation Unit, Hematology Centre, Karolinska University Hospital Solna, Stockholm, Sweden
2   Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet (KI), Stockholm, Sweden
7   Department of Proteomics, School of Biotechnology, Science for Life Laboratory, Royal Institute of Technology (KTH), Stockholm, Sweden
› Author Affiliations Financial support: The TEHS study was funded by Janssen-Cilag, Novartis, Organon, Schering, Wyeth, AFA, Centre for Gender Medicine and by the authors’ affiliations. The sponsors were not involved in the design and conduct of the study; collection, management, analysis or interpretation of the data, and preparation, review, or approval of the manuscript. Genotyping using the Illumina platform at the Uppsala University SNP genotyping platform was supported by Uppsala University, Uppsala University Hospital and the Swedish Research Council for Infrastructures. Genotyping and the work on this manuscript were supported by the Swedish Heart-Lung Foundation, the Swedish Research Council (8691), the Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council, the Foundation for Strategic Research and the Stockholm County Council (560283, 20130508). J. O. is supported by a joint grant from the Royal Institute of Technology and Stockholm County Council. R.J.S. is supported by the Strategic Research Program in Diabetes at Karolinska Institutet.
Further Information

Publication History

Received: 08 June 2015

Accepted after major revision: 29 August 2015

Publication Date:
22 November 2017 (online)

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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

 

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