Original ArticlesThe frequent Marburg I polymorphism impairs the pro-urokinase activating potency of the factor VII activating protease (FSAP)Roemisch, J.; Feussner, A.; Nerlich, C.; Stoehr, H.-A.; Weimer, T.Author Information The authors are with Aventis Behring GmbH, Preclinical Research & Development, Marburg, Germany. (Received 8 January 2002; revised 19 March 2002; accepted 3 April 2002) Address correspondence to Juergen Roemisch, Ph.D., Aventis Behring GmbH, Preclinical Research & Development, P.O Box 1230, 35002 Marburg, Germany. Tel: (+49) 6421 394414; fax: (+49) 6421 394663; e-mail: [email protected] Blood Coagulation & Fibrinolysis: July 2002 - Volume 13 - Issue 5 - p 433-441 Buy Abstract The recently reported plasmatic, Factor Seven Activating Protease (FSAP), has also been found to be a potent activator of pro-urokinase [single-chain plasminogen activator, urinary type (scuPA)]. An initial epidemiological study surprisingly showed that plasmas of 5–10% of healthy blood donors had an impaired potential to activate scuPA. Analysis of the respective genomic DNAs revealed one particular single nucleotide polymorphism of FSAP resulting in an identical amino acid exchange (G511E), which correlates with the reduced activities. The corresponding mutation was named FSAP Marburg I. Thrombelastographies of wild-type and mutant plasmas were performed, facilitating the auto-activation of the intrinsic FSAP pro-enzymes by addition of dextran sulfate (DXS) and accelerated clot lysis by addition of scuPA. On these conditions, tissue-factor-induced coagulation revealed that clot lysis was significantly delayed in the Marburg I mutant plasmas as compared with wild-type plasmas. Furthermore, in the presence of DXS and scuPA, a FSAP-deficient plasma revealed significantly prolonged plasma clot lysis times, whereas the addition of purified FSAP pro-enzyme plus scuPA reversed this effect. These results support the hypothesis that FSAP contributes to the scuPA-dependent plasma fibrinolytic potential, which can be impaired in plasmas containing the FSAP Marburg I polymorphism, for instance. © 2002 Lippincott Williams & Wilkins, Inc.