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Ward-Caviness, Cavin K.; Huffman, Jennifer E.; Everett, Karl; Germain, Marine; van Dongen, Jenny; Hill, W. David; Jhun, Min A.; Brody, Jennifer A.; Ghanbari, Mohsen; Du, Lei; Roetker, Nicholas S.; de Vries, Paul S.; Waldenberger, Melanie; Gieger, Christian; Wolf, Petra; Prokisch, Holger; Koenig, Wolfgang; O’Donnell, Christopher J.; Levy, Daniel; Liu, Chunyu; Truong, Vinh; Wells, Philip S.; Trégouët, David-Alexandre; Tang, Weihong; [...]

DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis

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  • Medientyp: E-Artikel
  • Titel: DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis
  • Beteiligte: Ward-Caviness, Cavin K.; Huffman, Jennifer E.; Everett, Karl; Germain, Marine; van Dongen, Jenny; Hill, W. David; Jhun, Min A.; Brody, Jennifer A.; Ghanbari, Mohsen; Du, Lei; Roetker, Nicholas S.; de Vries, Paul S.; Waldenberger, Melanie; Gieger, Christian; Wolf, Petra; Prokisch, Holger; Koenig, Wolfgang; O’Donnell, Christopher J.; Levy, Daniel; Liu, Chunyu; Truong, Vinh; Wells, Philip S.; Trégouët, David-Alexandre; Tang, Weihong; [...]
  • Erschienen: American Society of Hematology, 2018
  • Erschienen in: Blood
  • Sprache: Englisch
  • DOI: 10.1182/blood-2018-02-831347
  • ISSN: 0006-4971; 1528-0020
  • Schlagwörter: Cell Biology ; Hematology ; Immunology ; Biochemistry
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95% confidence interval, 0.001-0.007; P = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10−5) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.</jats:p>
  • Zugangsstatus: Freier Zugang