Association of the alpha-fibrinogen Thr312Ala polymorphism with poststrokemortality in subjects with atrial fibrillation

Background-The a-fibrinogen Thr312Ala polymorphism occurs in close proximit y to several sites important for factor XIIIa-dependent cross-linking, whic h 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 si gnificant difference in the genotype distributions of patients with acute i schemic stroke (n=519) and healthy control subjects (n=423), nor was there any association of this polymorphism with stroke subtype. In a Cox regressi on model, a significant interaction between Thr312Ala and atrial fibrillati on was identified in relation to poststroke mortality (P=0.002). In subject s in sinus rhythm (n=418), there was no difference according to genotype in the proportion of subjects who survived (approximate to 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 suscep tibility for embolization of intra-atrial clot, and these findings could ha ve important implications for identifying subjects most at risk of developi ng thromboembolic complications.