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

TitleCirculating ceruloplasmin, ceruloplasmin-associated genes and the incidence of venous thromboembolism in the Atherosclerosis Risk in Communities study.
Publication TypeJournal Article
Year of Publication2019
Authorsde Larriva APArenas, Alonso A, Norby FL, Roetker NS
Secondary AuthorsFolsom AR
JournalJ Thromb Haemost
Volume17
Issue5
Pagination818-826
Date Published2019 05
ISSN1538-7836
KeywordsAfrican Americans, Aged, Alleles, Atherosclerosis, Biomarkers, Ceruloplasmin, European Continental Ancestry Group, Female, Humans, Incidence, Male, Middle Aged, Polymorphism, Genetic, Proportional Hazards Models, Prospective Studies, Risk Factors, Venous Thromboembolism
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.

DOI10.1111/jth.14420
Alternate JournalJ Thromb Haemost
PubMed ID30803124
PubMed Central IDPMC6494693
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States