title: Functional analysis of the fibrinogen Aalpha Thr312Ala polymorphism: effects on fibrin structure and function.
abstract: BACKGROUND
  The fibrinogen Aalpha Thr312Ala polymorphism occurs within the alphaC domain of fibrinogen, which is important for lateral aggregation and factor XIII-induced cross-linking of fibrin fibers. We have previously shown an association of Ala312 fibrinogen with poststroke mortality in subjects with atrial fibrillation and with pulmonary embolism in subjects with venous thrombosis.
  
  
  RESULTS
  We studied the properties of clots formed from purified Ala312 and Thr312 fibrinogen and found that Ala312 fibrinogen produces stiffer clots, associated with increased alpha chain cross-linking, as demonstrated by SDS-Page. On electron microscopy analysis, we found larger fiber diameters in the Ala312 clots and observed a lower number of fibers per square micrometer. The number of branch points per square micrometer was similar between genotypes.
  
  
  CONCLUSIONS
  Our study shows that Ala312 influences clot structure and properties by increased factor XIII cross-linking and formation of thicker fibrin fibers. These findings may provide a mechanism by which Ala312 fibrinogen could predispose to clot embolization.
authors.affiliation: Academic Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, Leeds, UK.
authors.forename: Kristina F
authors.initials: KF
authors.lastname: Standeven
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grant
authors.forename: Angela M
authors.initials: AM
authors.lastname: Carter
authors.forename: Thomas
authors.initials: T
authors.lastname: Scheiner
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
authors.forename: Robert A S
authors.initials: RA
authors.lastname: Ariëns
mesh_terms: D001777:Blood Coagulation; D004548:Elasticity; D004591:Electrophoresis, Polyacrylamide Gel; D026122:Factor XIIIa / Q000378:metabolism; D005337:Fibrin / Q000502:physiology* / Q000648:ultrastructure*; D005340:Fibrinogen / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: C464794:fibrinogen Aalpha; D005337:Fibrin; D005340:Fibrinogen; D026122:Factor XIIIa