BACKGROUND AND AIMS: Variations in mixed platelet-leukocyte conjugate formation in human whole blood could be genetically determined. We quantified platelet and leukocyte activation and interaction in families with or without early myocardial infarction and evaluated their heritability, genetic correlation and linkage to the 9p21.3 region. METHODS AND RESULTS: The study population included 739 subjects (≥ 15 years old) from 54 large pedigrees, 23 with and 31 without familial myocardial infarction. Mixed platelet-leukocyte conjugates and markers of platelet or leukocyte activation (P-selectin, CD11b and L-selectin surface expression) were measured both before and after in vitro blood stimulation with collagen-ADP. All traits had significant genetic components (17.5-65.3% of the phenotypic variability), while shared household effects (0-39.6%) and environmental covariates (0-10.2%) tended to be smaller. Stimulated platelet-polymorphonuclear leukocyte (PMN) and platelet-monocyte conjugates showed the highest linkage to the 9p21.3 region (LOD = 0.94 and 1.33, respectively; empirical p value = 0.017 and 0.009). PMN markers resulted strongly genetically correlated between them in bivariate analysis among pairs of quantitative traits. CONCLUSION: This study supports a genetic regulation of human mixed platelet-leukocyte conjugates.
BACKGROUND AND AIMS: Variations in mixed platelet-leukocyte conjugate formation in human whole blood could be genetically determined. We quantified platelet and leukocyte activation and interaction in families with or without early myocardial infarction and evaluated their heritability, genetic correlation and linkage to the 9p21.3 region. METHODS AND RESULTS: The study population included 739 subjects (≥ 15 years old) from 54 large pedigrees, 23 with and 31 without familial myocardial infarction. Mixed platelet-leukocyte conjugates and markers of platelet or leukocyte activation (P-selectin, CD11b and L-selectin surface expression) were measured both before and after in vitro blood stimulation with collagen-ADP. All traits had significant genetic components (17.5-65.3% of the phenotypic variability), while shared household effects (0-39.6%) and environmental covariates (0-10.2%) tended to be smaller. Stimulated platelet-polymorphonuclear leukocyte (PMN) and platelet-monocyte conjugates showed the highest linkage to the 9p21.3 region (LOD = 0.94 and 1.33, respectively; empirical p value = 0.017 and 0.009). PMN markers resulted strongly genetically correlated between them in bivariate analysis among pairs of quantitative traits. CONCLUSION: This study supports a genetic regulation of human mixed platelet-leukocyte conjugates.
Authors: Fabrizia Noro; Francesco Gianfagna; Alessandro Gialluisi; Amalia De Curtis; Augusto Di Castelnuovo; Emanuela Napoleone; Chiara Cerletti; Maria Benedetta Donati; Giovanni de Gaetano; Marc F Hoylaerts; Licia Iacoviello; Benedetta Izzi Journal: Clin Epigenetics Date: 2019-05-10 Impact factor: 6.551
Authors: Benedetta Izzi; Alessandro Gialluisi; Francesco Gianfagna; Sabatino Orlandi; Amalia De Curtis; Sara Magnacca; Simona Costanzo; Augusto Di Castelnuovo; Maria Benedetta Donati; Giovanni de Gaetano; Marc F Hoylaerts; Chiara Cerletti; Licia Iacoviello Journal: Cells Date: 2021-10-13 Impact factor: 6.600
Authors: Benedetta Izzi; Francesco Gianfagna; Wen-Yi Yang; Katrien Cludts; Amalia De Curtis; Peter Verhamme; Augusto Di Castelnuovo; Chiara Cerletti; Maria Benedetta Donati; Giovanni de Gaetano; Jan A Staessen; Marc F Hoylaerts; Licia Iacoviello Journal: Clin Epigenetics Date: 2019-10-29 Impact factor: 6.551