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A plasma proteogenomic signature for fibromuscular dysplasia

dc.rights.licenseopenen_US
dc.contributor.authorOLIN, J. W.
dc.contributor.authorDI NARZO, A. F.
dc.contributor.authorD'ESCAMARD, V.
dc.contributor.authorKADIAN-DODOV, D.
dc.contributor.authorCHENG, H.
dc.contributor.authorGEORGES, A.
dc.contributor.authorKING, A.
dc.contributor.authorTHOMAS, A.
dc.contributor.authorBARWARI, T.
dc.contributor.authorMICHELIS, K. C.
dc.contributor.authorBOUCHAREB, R.
dc.contributor.authorBANDER, E.
dc.contributor.authorANYANWU, A.
dc.contributor.authorSTELZER, P.
dc.contributor.authorFILSOUFI, F.
dc.contributor.authorFLORMAN, S.
dc.contributor.authorCIVELEK, M.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.contributor.authorJEUNEMAITRE, X.
dc.contributor.authorBJORKEGREN, J. L. M.
dc.contributor.authorMAYR, M.
dc.contributor.authorBOUATIA-NAJI, N.
dc.contributor.authorHAO, K.
dc.contributor.authorKOVACIC, J. C.
dc.date.accessioned2021-02-24T11:14:48Z
dc.date.available2021-02-24T11:14:48Z
dc.date.issued2020
dc.identifier.issn1755-3245 (Electronic) 0008-6363 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26342
dc.description.abstractEnAims Fibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test. Methods and results Females with ‘multifocal’ FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios  = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%. Conclusion FMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease.
dc.language.isoENen_US
dc.subjectVINTAGE
dc.title.enA plasma proteogenomic signature for fibromuscular dysplasia
dc.title.alternativeCardiovasc Resen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/cvr/cvz219en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31424497en_US
bordeaux.journalCardiovascular Researchen_US
bordeaux.page63-77en_US
bordeaux.volume116en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamVINTAGEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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