Although venous thromboembolism (VTE) shows a polygenic nature, the crossroad between genome and environment is not fully understood. Genetics explains only a part of VTE hereditability and not defined molecular causes are found in approximately 50% of thrombotic patients. Thus, a major understanding of molecular mechanisms may clarify the missing hereditability. Concerning epigenetics, a particular histone modification (citrullination) plays a key role in increasing the rate of venous occlusive events by inducing neutrophil apoptosis and expulsion of neutrophil extra-cellular traps (NETs), which may be useful biomarkers of active disease. Moreover, an over-expression of miR-320a/b, miR-582, miR-195, miR-424-5p, and miR-532, or a down-regulation of miR495, miR-136-5p and miR-26a may improve the accuracy of VTE diagnosis. No clinical studies have focused on DNA methylation in VTE. Nowadays, no validated epigenetics biomarkers are routinely used for diagnosis and prevention of VTE. In the era of personalized therapy, several clinical trials are investigating the putative role of statins, a class of lipid-lowering epigenetic-based drugs, as additional therapeutic agents in VTE. Furthermore, single nucleotide polymorphisms (SNPs) in CYP2C9, VKORC1, and MIR133 genes can help physicians to predict individual warfarin dose requirement. Consequently, a comprehensive understanding of the mechanisms involved in the control of blood clot development is crucial to design novel therapeutic strategies. This review summarizes the current clinical concepts both in genetic and epigenetic VTE framework. Furthermore, we discuss the contribution of the innovative network medicine paradigm into advancing our knowledge about molecular underpinnings needed to support novel VTE diagnostic and therapeutic options.
Interplay between genetics and epigenetics in modulating the risk of venous thromboembolism: A new challenge for personalized therapy / G. Benincasa, D. Costa, T. Infante, R. Lucchese, F. Donatelli, C. Napoli. - In: THROMBOSIS RESEARCH. - ISSN 0049-3848. - 177(2019 May), pp. 145-153.
|Titolo:||Interplay between genetics and epigenetics in modulating the risk of venous thromboembolism: A new challenge for personalized therapy|
DONATELLI, FRANCESCO (Penultimo) [Membro del Collaboration Group]
|Parole Chiave:||Epigenetics, Network medicine, Personalized therapy, Venous thromboembolism, DNA polymorphism, Medical research, Epigenetic inheritance, Anticholesteremic agents, Cytochrome P-450, Medicine, Experimental, Single nucleotide polymorphisms, Thromboembolism, Methylation, Chromosomes|
|Settore Scientifico Disciplinare:||Settore MED/05 - Patologia Clinica|
Settore MED/11 - Malattie dell'Apparato Cardiovascolare
Settore MED/15 - Malattie del Sangue
Settore MED/23 - Chirurgia Cardiaca
|Data di pubblicazione:||mag-2019|
|Data ahead of print / Data di stampa:||2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.thromres.2019.03.008|
|Appare nelle tipologie:||01 - Articolo su periodico|