Association of the α-Fibrinogen Thr312Ala Polymorphism With Poststroke Mortality in Subjects With Atrial Fibrillation

BACKGROUND: The alpha-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 (approximately 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.