Complement activation assessed by the plasma terminal complement complex and future risk of venous thromboembolism
Author(s): ,
Ina I. Høiland
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
Correspondence |Ina I. Høiland, K. G. Jebsen, Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, N‐9037 Tromsø, Norway.|Email: ina.i.hoiland@uit.no
,
Robin A. Liang
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
,
Sigrid K. Brækkan
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
,
Kristin Pettersen
Affiliations:
Research Laboratory, Nordland Hospital, Bodø, Norway
,
Judith K. Ludviksen
Affiliations:
Research Laboratory, Nordland Hospital, Bodø, Norway
,
Nadezhda Latysheva
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
,
Omri Snir
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
,
Thor Ueland
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
,
Kristian Hindberg
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway
,
Tom E. Mollnes
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway. Research Laboratory, Nordland Hospital, Bodø, Norway. Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway
John‐Bjarne Hansen
Affiliations:
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT – The Arctic University of Norway, Tromsø, Norway. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
ISTH Academy. Hiland I. May 31, 2019; 273627
Ina Hiland
Ina Hiland
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Journal Abstract
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Background
It remains uncertain whether activation of the complement system, assessed by the soluble terminal C5b‐9 complement complex (plasma TCC), is associated with future risk of incident venous thromboembolism (VTE).
Objectives
To investigate the association between plasma levels of TCC and future risk of incident VTE in a nested case‐control study, and to explore genetic variants associated with TCC using protein quantitative trait loci analysis of exome sequencing data.
Methods
We sampled 415 VTE cases and 848 age‐ and sex‐matched controls from a population‐based cohort, the Tromsø study. Logistic regression models were used to calculate odds ratios with 95% confidence intervals for VTE across quartiles of plasma levels of TCC. Whole exome sequencing was conducted using the Agilent SureSelect 50 Mb capture kit.
Results
The risk of VTE increased across increasing quartiles of plasma TCC, particularly for unprovoked VTE. Participants with TCC in the highest quartile (>1.40 complement arbitrary units/mL) had an odds ratio for unprovoked VTE of 1.74 (95% confidence interval: 1.10–2.78) compared with those with TCC in the lowest quartile (≤0.80 complement arbitrary units/mL) in analyses adjusted for age, sex, and body mass index. A substantially higher risk for VTE was observed in samples taken shortly before VTE event. We found no association between genome‐wide or complement‐related gene variants and plasma levels of TCC.
Conclusions
We found that high levels of plasma TCC were associated with VTE risk, and unprovoked events in particular. There was no genome‐wide association between gene variants and plasma levels of TCC.
Keyword(s)
complement system, protein quantitative trait loci analysis, terminal complement complex, venous thromboembolism, whole exome sequencing
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