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Title: From genetics to epigenetics in platelet research
Authors: Freson, Kathleen ×
Izzi, Benedetta
Van Geet, Chris #
Issue Date: Jan-2012
Publisher: Pergamon Press
Series Title: Thrombosis Research vol:129 issue:3 pages:325-329
Abstract: Proteomic and genomic technologies have recently defined almost the complete platelet transcriptome and proteome as well as many important protein-protein interactions that are critical for platelet function under normal and pathological conditions such as an abnormal platelet function and cardiovascular disease (CVD). In contrast, the study of epigenetic processes such as DNA methylation and histone modification is still an unexplored domain in this research. Epigenetic marks are erased in early embryogenesis and reset during development. Environmental influences can lead to stable changes in the epigenome that alter the individual's susceptibility to disease. We will focus on the progress of DNA methylation studies in CVD. Techniques for genomic-scale analysis of DNA methylation became available but at the current stage however, several questions are still open as methylation marks are tissue-specific and it is not yet known whether leukocyte DNA reflects the correct epigenetic signature. It also remains uncertain if the observed associations of epigenetic profiles with disease are causative or just epiphenomena. Preliminary evidence exists that changes in DNA methylation can alter platelet activity as shown for the imprinted GNAS cluster that codes for the stimulatory G protein alpha subunit (Gs). Gs interacts with adenylyl cyclase to generate cAMP, which is inhibitory for platelet function. Patients with abnormal GNAS methylation have platelet Gs hypofunction and can develop risk for thrombosis and ischemic stroke at young age. This review is a brief introduction to these different aspects in epigenomics with a focus on DNA methylation in CVD and platelet research.
ISSN: 0049-3848
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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