Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 06 2023
07 06 2023
Historique:
received:
18
06
2022
accepted:
28
04
2023
medline:
9
6
2023
pubmed:
8
6
2023
entrez:
7
6
2023
Statut:
epublish
Résumé
Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
Identifiants
pubmed: 37286573
doi: 10.1038/s41467-023-38383-y
pii: 10.1038/s41467-023-38383-y
pmc: PMC10247781
doi:
Substances chimiques
Biomarkers
0
Complement Factor H
80295-65-4
Complement System Proteins
9007-36-7
Factor V
9001-24-5
CFHR5 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3280Subventions
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_13048
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C864/A14136
Pays : United Kingdom
Organisme : CSRD VA
ID : IK2 CX001780
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_21036
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-UU_12015/1
Pays : United Kingdom
Organisme : BLRD VA
ID : IK2 BX005759
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00006/1
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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