| Literature DB >> 30042098 |
Cavin K Ward-Caviness1,2, Jennifer E Huffman3,4,5, Karl Everett6, Marine Germain7,8, Jenny van Dongen9, W David Hill10,11, Min A Jhun12, Jennifer A Brody13,14, Mohsen Ghanbari15,16, Lei Du17, Nicholas S Roetker18, Paul S de Vries19, Melanie Waldenberger1,20, Christian Gieger20, Petra Wolf21, Holger Prokisch21,22, Wolfgang Koenig23,24,25, Christopher J O'Donnell4,26, Daniel Levy3,4, Chunyu Liu3,4, Vinh Truong6, Philip S Wells27, David-Alexandre Trégouët7,8, Weihong Tang18, Alanna C Morrison19, Eric Boerwinkle19,28, Kerri L Wiggins13,14, Barbara McKnight13,29, Xiuqing Guo30, Bruce M Psaty13,14,31,32,33, Nona Sotoodenia13,14,34, Dorret I Boomsma9, Gonneke Willemsen9, Lannie Ligthart9, Ian J Deary10,11, Wei Zhao12, Erin B Ware35, Sharon L R Kardia12, Joyce B J Van Meurs36, Andre G Uitterlinden36, Oscar H Franco15, Per Eriksson17, Anders Franco-Cereceda37, James S Pankow18, Andrew D Johnson3,4, France Gagnon6, Pierre-Emmanuel Morange38,39, Eco J C de Geus9,40, John M Starr10,41, Jennifer A Smith12,35, Abbas Dehghan15, Hanna M Björck17, Nicholas L Smith13,31,33,42, Annette Peters1.
Abstract
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.Entities:
Mesh：
Year: 2018 PMID： 30042098 PMCID： PMC6202911 DOI： 10.1182/blood-2018-02-831347
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113