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Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk

dc.rights.licenseopenen_US
dc.contributor.authorOLSON, N. C.
dc.contributor.authorRAFFIELD, L. M.
dc.contributor.authorLANGE, L. A.
dc.contributor.authorLANGE, E. M.
dc.contributor.authorLONGSTRETH, W. T., Jr.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHAUHAN, Ganesh
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorREINER, A. P.
dc.contributor.authorTRACY, R. P.
dc.date.accessioned2020-12-14T08:45:46Z
dc.date.available2020-12-14T08:45:46Z
dc.date.issued2018-01
dc.identifier.issn1538-7836 (Electronic) 1538-7836 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/21421
dc.description.abstractEnBACKGROUND: A fraction of coagulation factor VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). OBJECTIVE: Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke, and mortality. PATIENTS/METHODS: We measured FVIIa and FVIIa-AT in 3,486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n=2,410) and examined associations of FVII phenotypes with incident cardiovascular disease. RESULTS: In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa: beta= -25.9 mU/mL per minor allele; FVIIa-AT: beta= -26.6 pM per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa: beta= 7.8 mU/mL per minor allele; FVIIa-AT: beta= 9.9 per minor allele). Adjusted for risk factors, a 1-standard deviation higher FVIIa was associated with increased ischemic stroke risk (hazard ratio (HR) = 1.12; 95% confidence interval (CI): 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all-causes (HR: 1.08, 95% CI: 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR=0.69, 95% CI: 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. CONCLUSIONS: Results support the importance of the F7 and PROCR loci on variation in circulating FVIIa and FVIIa-AT. Findings suggest FVIIa is a risk factor for ischemic stroke in older adults while higher FVIIa-AT may reflect mortality risk.
dc.language.isoENen_US
dc.subject.enVINTAGE
dc.title.enAssociations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk
dc.title.alternativeJ Thromb Haemosten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1111/jth.13899en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed29112333en_US
bordeaux.journalJournal of Thrombosis and Haemostasisen_US
bordeaux.page19-30en_US
bordeaux.volume16en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03194200
hal.version1
hal.date.transferred2021-04-09T11:40:56Z
hal.exporttrue
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