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Blood, 15 January 2008, Vol. 111, No. 2, pp. 643-650. Prepublished online as a Blood First Edition Paper on October 9, 2007; DOI 10.1182/blood-2007-05-091231. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-091231v1 111/2/643    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ajjan, R. Articles by Ariëns, R. A. S. Search for Related Content PubMed PubMed Citation Articles by Ajjan, R. Articles by Ariëns, R. A. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Common variation in the C-terminal region of the fibrinogen β-chain: effects on fibrin structure, fibrinolysis and clot rigidity Ramzi Ajjan1, Bernard C. B. Lim2, Kristina F. Standeven1, Robert Harrand3, Sarah Dolling1, Fladia Phoenix1, Richard Greaves4, Radwa H. Abou-Saleh3, Simon Connell3, D. Alastair M. Smith3, John W. Weisel2, Peter J. Grant1, and Robert A. S. Ariëns1 1 Academic Unit of Molecular Vascular Medicine, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom; 2 Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Philadelphia; 3 Department of Physics, University of Leeds, Leeds, United Kingdom; and 4 Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom Fibrinogen BβArg448Lys is a common polymorphism, positioned within the carboxyl terminus of the Bβ-chain of the molecule. Studies suggest that it is associated with severity of coronary artery disease and development of stroke. The effects of the amino acid substitution on clot structure remains controversial, and the aim of this study was to investigate the effect(s) of this polymorphism on fibrin clot structure using recombinant techniques. Permeation, turbidity, and scanning electron microscopy showed that recombinant Lys448 fibrin had a significantly more compact structure, with thin fibers and small pores, compared with Arg448. Clot stiffness, measured by means of a novel method using magnetic tweezers, was significantly higher for the Lys448 compared with the Arg448 variant. Clots made from recombinant protein variants had similar lysis rates outside the plasma environment, but when added to fibrinogen-depleted plasma, the fibrinolysis rates for Lys448 were significantly slower compared with Arg448. This study demonstrates for the first time that clots made from recombinant BβLys448 fibrinogen are characterized by thin fibers and small pores, show increased stiffness, and appear more resistant to fibrinolysis. Fibrinogen BβArg448Lys is a primary example of common genetic variation with a significant phenotypic effect at the molecular level. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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