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Genome-wide analysi...
Genome-wide analysis of genetic determinants of circulating factorVII-activating protease (FSAP) activity
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- Olsson, Maja, 1975 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Stanne, Tara M, 1979 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Pedersen, Annie, 1981 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Lorentzen, Erik, 1974 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Core Facilities, Bioinformatics,Core Facilities, Bioinformatics
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- Kara, E. (författare)
- University of Oslo
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- Martinez-Palacian, A. (författare)
- University of Oslo
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- Sand, N. P. R. (författare)
- University of Southern Denmark,Hospital of South West Jutland, Esbjerg
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- Jacobsen, A. F. (författare)
- Oslo university hospital,University of Oslo
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- Sandset, P. M. (författare)
- University of Oslo,Oslo university hospital
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- Sidelmann, J. J. (författare)
- University of Southern Denmark
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- Engström, G. (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups
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- Melander, O. (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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- Kanse, S. M. (författare)
- University of Oslo
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- Jern, Christina, 1962 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- Engelska.
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 16:10, s. 2024-2034
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Abstract
Ämnesord
Stäng
- Background FactorVII-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- blood coagulation factors
- epidemiology
- genetic variation
- hemostasis
- plasma
- marburg-i polymorphism
- recurrent venous thromboembolism
- vascular
- smooth-muscle
- factor-vii
- ischemic-stroke
- oral-contraceptives
- neointima formation
- cell-proliferation
- liver fibrosis
- tissue factor
- Hematology
- Cardiovascular System & Cardiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Olsson, Maja, 19 ...
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Stanne, Tara M, ...
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Pedersen, Annie, ...
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Lorentzen, Erik, ...
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Kara, E.
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Martinez-Palacia ...
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Sand, N. P. R.
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Jacobsen, A. F.
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Sandset, P. M.
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Sidelmann, J. J.
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Engström, G.
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Melander, O.
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Kanse, S. M.
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Jern, Christina, ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Kardiologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Hematologi
- Artiklar i publikationen
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Journal of Throm ...
- Av lärosätet
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Göteborgs universitet
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Lunds universitet