Circulating ceruloplasmin, ceruloplasmin-associated genes and the incidence of venous thromboembolism in the Atherosclerosis Risk in Communities study

Antonio P. Arenas de Larriva, Alvaro Alonso, Faye Norby, Nicholas S. Roetker, Aaron R Folsom

Research output: Contribution to journalArticlepeer-review

Abstract

Essentials Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed associations between CP and venous thromboembolism (VTE) risk in 9933 individuals. Higher circulating CP but not CP-related genes were associated with greater incident VTE rates. Circulating CP could be considered a non-causal biomarker of VTE risk in the community. Summary: Background Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed the associations between CP, CP-associated genetic variants and incident venous thomboembolism (VTE) in the Atherosclerosis Risk in Communities study. Methods and results In an observational study, 9933 men and women aged 53–75 years without prevalent VTE were included in 1996–1998 and followed through 2011. Circulating CP was measured in stored blood samples obtained in 1996–1998. Polymorphisms rs11708215 and rs13072552, which have been previously associated with CP concentrations, were measured in 8439 participants. VTEs were identified from hospital discharge codes and validated by physician review of medical records and imaging reports. Over a mean of 10.5 years of follow-up, 376 cases of VTE were identified. The association between circulating CP, CP-associated polymorphisms and the incidence of VTE was estimated. After adjustment for traditional risk factors and biomarkers, higher concentrations of circulating CP were associated with greater incident VTE rates (hazard ratio 1.82, 95% confidence interval 1.12–2.95, comparing the 87.5–100th percentile with the bottom quartile). Both rs11708215 and rs13072552 were associated with CP concentrations but not with VTE risk. Conclusions Even though high CP concentrations were associated with an increased VTE risk, CP-associated genetic variants were not associated with a higher risk of VTE. Our results suggest that circulating CP concentrations may not be causally related to the risk of incident VTE.

Original languageEnglish (US)
Pages (from-to)818-826
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume17
Issue number5
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
The ARIC Study is carried out as a collaborative study supported by: National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268 201100009C, HHSN268201100010C, HHSN268201100011 C, and HHSN268201100012C), R01HL087641, R01H L59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. The infrastructure was partly supported by Grant Number UL1RR02500 5, a component of the National Institutes of Health and NIH Roadmap for Medical Research.

Funding Information:
The ARIC Study is carried out as a collaborative study supported by: National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. The infrastructure was partly supported by Grant Number UL1RR02500 5, a component of the National Institutes of Health and NIH Roadmap for Medical Research.

Publisher Copyright:
© 2019 International Society on Thrombosis and Haemostasis

Keywords

  • ceruloplasmin
  • oxidative stress
  • single-nucleotide polymorphism
  • venous thromboembolism

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