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

Abstract

Background —The α-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.