A M Carter1, A J Catto, P J Grant. 1. Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, UK.
Abstract
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.
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.
Authors: Christina L Wassel; Leslie A Lange; Brendan J Keating; Kira C Taylor; Andrew D Johnson; Cameron Palmer; Lindsey A Ho; Nicholas L Smith; Ethan M Lange; Yun Li; Qiong Yang; Joseph A Delaney; Weihong Tang; Geoffrey Tofler; Susan Redline; Herman A Taylor; James G Wilson; Russell P Tracy; David R Jacobs; Aaron R Folsom; David Green; Christopher J O'Donnell; Alexander P Reiner Journal: Blood Date: 2010-10-26 Impact factor: 22.113
Authors: S L Zhang; W DuBois; E S Ramsay; V Bliskovski; H C Morse; L Taddesse-Heath; W C Vass; R A DePinho; B A Mock Journal: Mol Cell Biol Date: 2001-01 Impact factor: 4.272
Authors: James F Meschia; Thomas G Brott; Robert D Brown; Richard J P Crook; Michael Frankel; John Hardy; José G Merino; Stephen S Rich; Scott Silliman; Bradford Burke Worrall Journal: BMC Neurol Date: 2003-07-08 Impact factor: 2.474