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.