(Circulation. 1999;99:2423-2426.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Association of the 
-Fibrinogen Thr312Ala Polymorphism With Poststroke Mortality in Subjects With Atrial Fibrillation
From the Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, UK.
Correspondence to Peter J. Grant, Unit of Molecular Vascular Medicine, Research School of Medicine, G Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, UK. E-mail p.j.grant{at}leeds.ac.uk
Background—The 
-fibrinogen
Thr312Ala polymorphism occurs in close proximity to several sites
important for factor XIIIa–dependent cross-linking, which raises the
possibility that it affects fibrin clot stability.
Methods and Results—We determined the association of this
polymorphism with ischemic stroke, stroke subtype, and
poststroke mortality. There was no significant difference in the
genotype distributions of patients with acute ischemic
stroke (n=519) and healthy control subjects (n=423), nor was there any
association of this polymorphism with stroke subtype. In a Cox
regression model, a significant interaction between Thr312Ala and
atrial fibrillation was identified in relation to poststroke mortality
(P=0.002). In subjects in sinus rhythm (n=418), there
was no difference according to genotype in the proportion of
subjects who survived (
60% in each group), whereas in subjects with
atrial fibrillation (n=101), there was decreased survival in those
possessing the A allele (TT=42.1%, TA=18%, AA=0%).
Conclusions—The Thr312Ala polymorphism may give rise to an increased susceptibility for embolization of intra-atrial clot, and these findings could have important implications for identifying subjects most at risk of developing thromboembolic complications.
Key Words: stroke • mortality • atrial fibrillation
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