Contributors: Science for Life Laboratory Solna; KTH Royal Institute of Technology Stockholm (KTH); University Hospital of North Norway Tromsø (UNN); The Arctic University of Norway Tromsø, Norway (UiT); Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Assistance Publique - Hôpitaux de Marseille (APHM); Bordeaux population health (BPH); Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM); Karolinska Institute; Karolinska University Hospital Solna, Sweden (KUH); National Heart, Lung, and Blood Institute Bethesda (NHLBI); Framingham Heart Study; Boston University Boston (BU)-National Heart, Lung, and Blood Institute Bethesda (NHLBI); Medizinische Universität Wien = Medical University of Vienna; Centre National de Recherche en Génomique Humaine (CNRGH); Institut de Biologie François JACOB (JACOB); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); University of Cambridge UK (CAM); Charité - UniversitätsMedizin = Berlin University Medicine; Queen Mary University of London (QMUL); Perelman School of Medicine; University of Pennsylvania; Veterans Affairs Palo Alto Healthcare System; Stanford University; University of Washington Seattle; Kaiser Permanente Washington Health Research Institute Seattle (KPWHRI); Seattle Epidemiologic Research and Information Center Seattle; Hôpital Européen Georges Pompidou APHP (HEGP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO); Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Karolinska University Hospital Stockholm; Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf Hamburg (UKE); University Medical Center of the Johannes Gutenberg-University Mainz; Royal College of Surgeons in Ireland (RCSI); Hospital de la Santa Creu i Sant Pau; Centre for Research in Epidemiology and Statistics; Conservatoire National des Arts et Métiers CNAM (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Centre d'Etude du Polymorphisme Humain (CEPH); Institut Universitaire d'Hématologie (IUH); Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université Paris Cité (UPCité); Royal Institute of Technology; ANR-17-EURE-0019,DPH,University of Bordeaux Graduate School in Digital Public Health(2017)
نبذة مختصرة : International audience ; 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.
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