Sidelmann Johannes J, Vitzthum Frank, Funding Eva, Münster Anna-Marie B, Gram Jørgen, Jespersen Jørgen
Institute of Public Health, University of Southern Denmark, Niels Bohrs Vej 9, DK-6700 Esbjerg, Denmark.
Thromb Res. 2008;122(6):848-53. doi: 10.1016/j.thromres.2008.02.002. Epub 2008 Apr 18.
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.
凝血因子VII激活蛋白酶（FSAP）参与止血和炎症过程。FSAP可裂解单链尿激酶型纤溶酶原激活剂（scu-PA）。FSAP基因中1601G/A多态性的1601GA基因型导致表达一种激活scu-PA能力降低的FSAP变体，而不影响激活凝血因子VII（FVII）的能力。以往研究调查了1601GA基因型与颈动脉狭窄和深静脉血栓形成（DVT）的发生率及进展之间的关联。本研究首次评估FSAP表型与DVT之间的潜在关联。我们研究了170例疑似DVT患者血浆中1601G/A多态性、FSAP活性、FSAP抗原、凝血因子VIIa（FVIIa）、凝血酶原片段1+2（F1+2）和C反应蛋白（CRP）之间的关联。FSAP基因型在有DVT（n=64）和无DVT（n=106）的患者中分布相同（P=0.94）。1601GA基因型与FSAP活性显著降低（P<0.001）和FSAP抗原水平降低（P=0.04）相关。与无DVT的患者相比，DVT患者的FSAP活性（P=0.008）、FSAP抗原（P=0.003）和F1+2水平显著更高（P<0.001）。当校正CRP水平后，FSAP指标与DVT之间的关联消失。F1+2与FSAP抗原呈正相关（P=0.01），而有DVT和无DVT患者的FVIIa水平相当。我们得出结论，尽管急性DVT患者的FSAP指标显著升高，但FSAP激活scu-PA特性的改变可能并未显著参与急性DVT的发生发展，且校正CRP后FSAP与DVT之间的关联消失。
