BACKGROUND: Activation markers of coagulation and fibrinolysis are increased in individuals at risk of coronary-artery disease and other thrombotic disorders--a condition defined as the prethrombotic state. We aimed to find out the extent to which the prethrombotic state is determined by genetic factors. METHODS: We analysed concentrations of prothrombin, prothrombin fragment 1+2, thrombin-antithrombin complex, crosslinked fibrin degradation product D-dimer, and thrombin-activatable fibrinolysis inhibitor by ELISA in 118 monozygotic and 112 dizygotic unselected female twins aged 21-73 years from the St Thomas' UK Adult Twin Registry. We used quantitative genetic-model fitting to estimate heritability. FINDINGS: We found significant heritabilities in concentrations of the activation markers in plasma. Genetic factors contributed 45, 40, and 65% of the variation in concentrations of fragment 1+2, thrombin-antithrombin complex, and D-dimer, respectively. Age was important only in fragment 1+2 concentrations, in which it accounted for 12% of the variation. The remaining variation could be attributed to unique environmental factors. Variation in concentrations of precursor prothrombin in plasma was determined by 57% heritability, and that of zymogen thrombin-activatable fibrinolysis inhibitor showed a very strong genetic component (82%). INTERPRETATION: The activation mechanisms of the coagulation and fibrinolytic systems, and therefore the prethrombotic state, are controlled to a substantial degree by genetic factors. Genes influencing activation of haemostasis are likely to be an important component of the overall thrombotic tendency in the general population.
BACKGROUND: Activation markers of coagulation and fibrinolysis are increased in individuals at risk of coronary-artery disease and other thrombotic disorders--a condition defined as the prethrombotic state. We aimed to find out the extent to which the prethrombotic state is determined by genetic factors. METHODS: We analysed concentrations of prothrombin, prothrombin fragment 1+2, thrombin-antithrombin complex, crosslinked fibrin degradation product D-dimer, and thrombin-activatable fibrinolysis inhibitor by ELISA in 118 monozygotic and 112 dizygotic unselected female twins aged 21-73 years from the St Thomas' UK Adult Twin Registry. We used quantitative genetic-model fitting to estimate heritability. FINDINGS: We found significant heritabilities in concentrations of the activation markers in plasma. Genetic factors contributed 45, 40, and 65% of the variation in concentrations of fragment 1+2, thrombin-antithrombin complex, and D-dimer, respectively. Age was important only in fragment 1+2 concentrations, in which it accounted for 12% of the variation. The remaining variation could be attributed to unique environmental factors. Variation in concentrations of precursor prothrombin in plasma was determined by 57% heritability, and that of zymogen thrombin-activatable fibrinolysis inhibitor showed a very strong genetic component (82%). INTERPRETATION: The activation mechanisms of the coagulation and fibrinolytic systems, and therefore the prethrombotic state, are controlled to a substantial degree by genetic factors. Genes influencing activation of haemostasis are likely to be an important component of the overall thrombotic tendency in the general population.
Authors: Virginia M Miller; Tanya M Petterson; Elysia N Jeavons; Abhinita S Lnu; David N Rider; John A Heit; Julie M Cunningham; Gordon S Huggins; Howard N Hodis; Matthew J Budoff; Nanette Santoro; Paul N Hopkins; Rogerio A Lobo; JoAnn E Manson; Frederick Naftolin; Hugh S Taylor; S Mitchell Harman; Mariza de Andrade Journal: Physiol Genomics Date: 2012-11-27 Impact factor: 3.107
Authors: Lu-Chen Weng; Weihong Tang; Stephen S Rich; Nicholas L Smith; Susan Redline; Christopher J O'Donnell; Saonli Basu; Alexander P Reiner; Joseph A Delaney; Russell P Tracy; Cameron D Palmer; Taylor Young; Qiong Yang; Aaron R Folsom; Mary Cushman Journal: Thromb Res Date: 2014-05-20 Impact factor: 3.944
Authors: Maria Sabater-Lleal; Alfonso Buil; Juan Carlos Souto; Laura Alamsy; Montserrat Borrell; Mark Lathrop; John Blangero; Jordi Fontcuberta; José Manuel Soria Journal: Hum Genet Date: 2008-06-18 Impact factor: 4.132
Authors: Frances M K Williams; Angela M Carter; Bernet Kato; Mario Falchi; Lise Bathum; Gabriela Surdulescu; Kirsten Ohm Kyvik; Aarno Palotie; Tim D Spector; Peter J Grant Journal: Arterioscler Thromb Vasc Biol Date: 2009-01-15 Impact factor: 8.311
Authors: Augusto Di Castelnuovo; Amalia de Curtis; Simona Costanzo; Mariarosaria Persichillo; Marco Olivieri; Francesco Zito; Maria Benedetta Donati; Giovanni de Gaetano; Licia Iacoviello Journal: Haematologica Date: 2013-05-03 Impact factor: 9.941