title: Factor VII-activating protease in patients with acute deep venous thrombosis.
abstract: Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu-PA, without affecting the ability to activate coagulation Factor VII (FVII). Previous studies have investigated the association of the 1601GA genotype with incidence and progression of carotid stenosis and deep venous thrombosis (DVT). The present study is the first to evaluate the potential association between the FSAP phenotype and DVT. We studied the association between the 1601G/A polymorphism, FSAP activity, FSAP antigen, Factor VIIa (FVIIa), prothrombin fragment 1+2 (F1+2), and C-reactive protein (CRP) in plasmas of 170 patients suspected for DVT. FSAP genotypes were equally distributed in patients with (n=64) and without DVT (n=106), (P=0.94). The 1601GA genotype was associated with significant reduction of FSAP activity (P<0.001) and FSAP antigen levels (P=0.04). Patients with DVT showed significantly higher FSAP activity (P=0.008), FSAP antigen (P=0.003), and F1+2 levels (P<0.001) than patients without DVT. The association between the FSAP measures and DVT disappeared when adjusted for CRP levels. F1+2 correlated positively to FSAP antigen (P=0.01), while FVIIa-levels were comparable in patients with and without DVT. We conclude that even though FSAP measures are significantly increased in patients with acute DVT, alterations in the scu-PA activating properties of FSAP are presumably not markedly involved in the development of acute DVT, and that the association between FSAP and DVT disappears after adjustment for CRP.
authors.affiliation: Institute of Public Health, University of Southern Denmark, Niels Bohrs Vej 9, DK-6700 Esbjerg, Denmark. Johannes.Sidelmann@svs.regionsyddanmark.dk
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Sidelmann
authors.forename: Frank
authors.initials: F
authors.lastname: Vitzthum
authors.forename: Eva
authors.initials: E
authors.lastname: Funding
authors.forename: Anna-Marie B
authors.initials: AM
authors.lastname: Münster
authors.forename: Jørgen
authors.initials: J
authors.lastname: Gram
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jespersen
mesh_terms: D000208:Acute Disease; D002097:C-Reactive Protein / Q000032:analysis; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D012697:Serine Endopeptidases / Q000097:blood* / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood* / Q000209:etiology
chemical_list: D002097:C-Reactive Protein; C433550:HABP2 protein, human; D012697:Serine Endopeptidases