Abstract
BackgroundEpigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in processes underlying cardiovascular disease (CVD), including atherosclerosis, inflammation, hypertension and diabetes. MethodsEleven databases were searched for studies investigating the association between epigenetic marks (either global, site-specific or genome-wide methylation of DNA and histone modifications) and CVD. ResultsOf the 3459 searched references, 31 studies met our inclusion criteria (26 cross-sectional studies and 5 prospective studies). Overall, 12,648 individuals were included, with total of 4037 CVD events. The global DNA methylation assessed at long-interspersed nuclear element (LINE-1) was inversely associated with CVD, independent of established cardiovascular risk factors. Conversely, a higher degree of global DNA methylation measured at Alu repeats or by the LUMA method was associated with the presence of CVD. The studies reported epigenetic regulation of 34 metabolic genes (involved in fetal growth, glucose and lipid metabolism, inflammation, atherosclerosis and oxidative stress) in blood cells to be related with CVD. Among them, 5 loci were validated and methylation at F2RL3 was reported in two large prospective studies to predict cardiovascular disease beyond the traditional risk factors. ConclusionsCurrent evidence supports an association between genomic DNA methylation and CVD. However, this review highlights important gaps in the existing evidences including lack of large-scale epigenetic investigations, needed to reliably identify genomic loci where DNA methylation is related to risk of CVD.
Highlights
There is a worldwide epidemic of cardiovascular disease (CVD) causing one-third of all deaths worldwide and counting for trillions of dollars of health care expenditure [1,2]
Our findings indicate that global DNA methylation might influence CVD risk and this could occur beyond the traditional cardiovascular risk factors
Some studies show that supplementation with methyl donors such as folate, choline and vitamin B12 may influence DNA methylation and may have a beneficial effect on CVD risk, but results are still inconsistent [81,82,83,84]
Summary
There is a worldwide epidemic of cardiovascular disease (CVD) causing one-third of all deaths worldwide and counting for trillions of dollars of health care expenditure [1,2]. DNA methylation and histone modifications are the best understood of the epigenetic mechanisms far [4], and have been suggested to regulate gene expression and affect CVD risk factors including atherosclerosis, inflammation, hypertension and diabetes [5,6,7]. Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in processes underlying cardiovascular disease (CVD), including atherosclerosis, inflammation, hypertension and diabetes. Methods: Eleven databases were searched for studies investigating the association between epigenetic marks (either global, site-specific or genome-wide methylation of DNA and histone modifications) and CVD. This review highlights important gaps in the existing evidences including lack of large-scale epigenetic investigations, needed to reliably identify genomic loci where DNA methylation is related to risk of CVD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
