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dc.date.accessioned2020-02-07T19:26:50Z
dc.date.available2020-02-07T19:26:50Z
dc.date.created2018-08-30T09:17:43Z
dc.date.issued2018
dc.identifier.citationOlsson, Maja Stanne, Tara M. Pedersén, Annie Lorentzen, Erik Kara, Emrah Martinez-Palaciàn, Adoraciòn Rønnow Sand, Niels Peter Jacobsen, Anne Flem Sandset, Per Morten Sidelmann, Johannes Jakobsen Engström, Gunnar Melander, Olle Kanse, Sandip Jern, Christina . Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity.. Journal of Thrombosis and Haemostasis. 2018, 16(10), 2024-2034
dc.identifier.urihttp://hdl.handle.net/10852/72853
dc.description.abstractBackground Factor VII‐activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low‐frequency missense variant Marburg‐I (rs7080536) in the FSAP‐encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome‐wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene‐based tests. Using GWAS, we confirmed the strong association between the Marburg‐I variant and FSAP activity. HABP2 was also significant in the gene‐based analysis, and remained significant after exclusion of Marburg‐I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg‐I carriers, and this finding was replicated. A secondary genome‐wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg‐I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity.
dc.languageEN
dc.publisherBlackwell Publishing
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.titleGenome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity.
dc.typeJournal article
dc.creator.authorOlsson, Maja
dc.creator.authorStanne, Tara M.
dc.creator.authorPedersén, Annie
dc.creator.authorLorentzen, Erik
dc.creator.authorKara, Emrah
dc.creator.authorMartinez-Palaciàn, Adoraciòn
dc.creator.authorRønnow Sand, Niels Peter
dc.creator.authorJacobsen, Anne Flem
dc.creator.authorSandset, Per Morten
dc.creator.authorSidelmann, Johannes Jakobsen
dc.creator.authorEngström, Gunnar
dc.creator.authorMelander, Olle
dc.creator.authorKanse, Sandip
dc.creator.authorJern, Christina
cristin.unitcode185,51,12,10
cristin.unitnameSeksjon for Biokjemi
cristin.ispublishedtrue
cristin.fulltextpreprint
cristin.qualitycode1
dc.identifier.cristin1605444
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Thrombosis and Haemostasis&rft.volume=16&rft.spage=2024&rft.date=2018
dc.identifier.jtitleJournal of Thrombosis and Haemostasis
dc.identifier.volume16
dc.identifier.issue10
dc.identifier.startpage2024
dc.identifier.endpage2034
dc.identifier.doihttps://doi.org/10.1111/jth.14258
dc.identifier.urnURN:NBN:no-75997
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn1538-7933
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/72853/2/Olsson_et_al-2018-Journal_of_Thrombosis_and_Haemostasis.pdf
dc.type.versionPublishedVersion


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