alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism

The A alpha-fibrinogen Thr312Ala polymorphism, which occurs in a region inv olved in factor XIII (FXIII)-dependent cross-linking processes, is associat ed with poststroke mortality in subjects with atrial fibrillation, suggesti ng an influence either on intraatrial clot formation or embolization, We ha ve determined the association of Thr312Ala with deep vein thrombosis (DVT) and pulmonary embolism (PE) and have assessed the interaction of Thr312Ala with the FXIII Val34Leu polymorphism in 122 patients with DVT, 99 patients with PE, and 254 healthy control subjects. The genotype distribution of pat ients with PE (TT = 49%, TA = 36%, AA=75%), but not DVT (TT = 50%, TA = 42% , AA = 8%), differed significantly from healthy control subjects (TT = 60%, TA = 34%, AA = 6%, P = .02), A significant interaction of Thr312Ala and Va l34Leu was also identified (P = .01), indicating an inverse association bet ween Leu34 and Ala312, These results support the hypothesis that Thr312Ala alters FXIII-dependent cross-linking, making formed fibrin clot more suscep tible to embolization. (C) 2000 by The American Society of Hematology.