Heritability, genetic correlation and linkageto the 9p21.3 region of mixed platelet-leukocyte conjugates in families with and without early myocardial infarction

F. Gianfagna, C. Tamburrelli, B. Vohnout, M. Crescente, B. Izzi, A. Pampuch, A. De Curtis, A. Di Castelnuovo, A. Cutrone, E. Napoleone, B. Tayo, R. Lorenzet, L. Nanni, M. Arca, M. B. Donati, G. de Gaetano, C. Cerletti, L. Iacoviello

Research output: Contribution to journalArticlepeer-review

Abstract

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 invitro 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%) tendedto be smaller. Stimulated platelet-polymorphonuclear leukocyte (PMN) andplatelet-monocyteconjugates 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.

Original languageEnglish
Pages (from-to)684-692
Number of pages9
JournalNutrition, Metabolism and Cardiovascular Diseases
Volume23
Issue number7
DOIs
Publication statusPublished - 2013

Keywords

  • Chromosome 9 genetics
  • Leukocytes
  • Linkage studies
  • Mixed aggregates
  • Platelet

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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