The role of thrombin activatable fibrinolysis inhibitor in arterial thrombosis at a young age: The ATTAC study
Journal of Thrombosis and Haemostasis , Volume 7 - Issue 6 p. 919- 927
Background and objectives: Thrombin activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and may therefore contribute to the pathophysiology of arterial thrombosis. The aim of the present study was to elucidate the pathogenetic role of TAFI levels and genotypes in young patients with arterial thrombosis. Patients and methods: In a case-control study, 327 young patients with a recent first-ever event of coronary heart disease (CHD subgroup) or cerebrovascular disease (ischemic stroke subgroup) and 332 healthy young controls were included. TAFI levels [intact TAFI, activation peptide (TAFI-AP) and (in)activated TAFI (TAFIa(i)] and TAFI activity were measured and genetic variations in the TAFI gene (-438G/A, 505G/A and 1040C/T) were determined. Results: In the total group of patients, TAFIa(i) levels were higher (145.1 ± 37.5%) than in controls (137.5 ± 31.3%, P = 0.02). Plasma levels of intact TAFI, TAFI-AP and TAFI activity were similar in patients and controls. In the CHD subgroup (n = 218), intact TAFI levels were higher (109.4 ± 23.0%) than in controls (102.8 ± 20.7%, P = 0.02). In 325Ile/Ile homozygotes, lower TAFI levels and a decreased risk of arterial thrombosis were observed (OR 0.58, 95% CI 0.34-0.99) compared with patients with the common 325Thr/Thr genotype. This association was most evident in CHD patients (OR 0.48, 95% CI 0.26-0.90). Haplotype analyses supported a role for the Thr325Ile polymorphism. Conclusions: TAFIa(i) levels were higher in patients with cardiovascular disease. Furthermore, the TAFI 325Thr/Ile polymorphism was associated with lower TAFI levels and with the risk of cardiovascular disease in young patients, especially in CHD.
|Coronary heart disease, DNA polymorphism, Fibrinolysis, Gene polymorphisms, Ischemic stroke, Premature atherosclerosis, Thrombin activatable fibrinolysis inhibitor, adult, artery thrombosis, article, cardiovascular risk, case control study, cerebrovascular accident, clinical trial, controlled clinical trial, controlled study, enzyme activity, female, fibrinolysis, genetic association, genetic variability, genotype, haplotype, human, ischemic heart disease, major clinical study, male, pathophysiology, priority journal, protein blood level, protein expression, risk assessment|
|Journal of Thrombosis and Haemostasis|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
de Bruijne, E.L.E, Gils, A, Guimarães, A.H.C, Dippel, D.W.J, Deckers, J.W, van den Meiracker, A.H, … Leebeek, F.W.G. (2009). The role of thrombin activatable fibrinolysis inhibitor in arterial thrombosis at a young age: The ATTAC study. Journal of Thrombosis and Haemostasis, 7(6), 919–927. doi:10.1111/j.1538-7836.2009.03350.x