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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5286-5292. Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2007-01-065185. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-01-065185v1 109/12/5286    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Christiansen, V. J. Articles by McKee, P. A. Search for Related Content PubMed PubMed Citation Articles by Christiansen, V. J. Articles by McKee, P. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The effect of a single nucleotide polymorphism on human 2-antiplasmin activity Victoria J. Christiansen1, Kenneth W. Jackson1, Kyung N. Lee1, and Patrick A. McKee1 1 William K. Warren Medical Research Center and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City The primary inhibitor of plasmin, 2-antiplasmin (2AP), is secreted by the liver into plasma with Met as the amino-terminus. During circulation, Met-2AP is cleaved by antiplasmin-cleaving enzyme (APCE), yielding Asn-2AP, which is crosslinked into fibrin approximately 13 times faster than Met-2AP. The Met-2AP gene codes for either Arg or Trp as the sixth amino acid, with both polymorphic forms found in human plasma samples. We determined the Arg6Trp genotype frequency in a healthy population and its effects on Met-2AP cleavage and fibrinolysis. Genotype frequencies were RR 62.5%, RW 34.0%, and WW 3.5%. The polymorphism related to the percentage of Met-2AP in plasma was WW (56.4%), RW (40.6%), and RR (23.6%). WW plasma tended to have shorter lysis times than RR and RW plasmas. APCE cleaved purified Met-2AP(Arg6) approximately 8-fold faster than Met-2AP(Trp6), which is reflected in Asn-2AP/Met-2AP ratios with time in RR, RW, and WW plasmas. Removal of APCE from plasma abrogated cleavage of Met-2AP. We conclude that the Arg6Trp polymorphism is functionally significant, as it clearly affects conversion of Met-2AP to Asn-2AP, and thereby, the rate of 2AP incorporation into fibrin. Therefore, the Arg6Trp polymorphism may play a significant role in governing the long-term deposition/removal of intravascular fibrin. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. H. P. Law, T. Sofian, W.-T. Kan, A. J. Horvath, C. R. Hitchen, C. G. Langendorf, A. M. Buckle, J. C. Whisstock, and P. B. Coughlin X-ray crystal structure of the fibrinolysis inhibitor {alpha}2-antiplasmin Blood, February 15, 2008; 111(4): 2049 - 2052. [Abstract] [Full Text] [PDF]

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