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

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; Morrison, Alanna C; Boerwinkle, Eric; Wiggins, Kerri L; McKnight, Barbara; Guo, Xiuqing; Psaty, Bruce M; Sotoodenia, Nona; Boomsma, Dorret I; Willemsen, Gonneke; Ligthart, Lannie; Deary, Ian J; Zhao, Wei; Ware, Erin B; Kardia, Sharon L R; Van Meurs, Joyce B J; Uitterlinden, Andre G; Franco, Oscar H; Eriksson, Per; Franco-Cereceda, Anders; Pankow, James S; Johnson, Andrew D; Gagnon, France; Morange, Pierre-Emmanuel; de Geus, Eco J C; Starr, John M; Smith, Jennifer A.
Blood; 132(17): 1842-1850, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30042098
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.
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