Monday, October 5, 2020

Epigenetics and Heart Disease

 
Researchers have recently found epigenetic applicability to establishing a patient’s cardiovascular risk.  Methylation, the epigenetic modification investigated in this study, is a mechanism utilizing the transfer of methyl groups onto the cytosine of specific DNA sequences. These methyl groups then allow for the recruitment of other proteins involved in down regulating gene expression or interfere with binding of transcription factors necessary to promote gene expression. This epigenetic modification is reversible and can be heavily influenced by environmental factors (Moore et. al.)

Prior to the study in question, only small cohorts had been evaluated for CPG island methylation status correlated with estimating one’s cardiac risk.  This study utilized blood DNA samples from multiple cohort studies in both the United States and Europe to evaluate epigenome-wide modification of leukocytes in cardiovascular disease. Areas that were associated with coronary heart disease were in found genes that play a part in calcium regulation, coronary artery calcified plaque, and kidney function. Additionally, Mendelian randomization analysis showed a causal effect of DNA methylation in regulatory regions, both in non-coding RNA and genes that play a role in normal cellular structure and function. These findings highlight the clinical utility of methylation states, as well as identifying less-emphasized pathways in calcium regulation and kidney function that may significantly contribute to coronary heart disease. This could lead to new therapeutic targets, new prevention strategies, and novel diagnostic tools.

 

Agha, G., Mendelson, M. M., Ward-Caviness, C. K., Joehanes, R., Huan, T., Gondalia, R., Salfati, E., Brody, J. A., Fiorito, G., Bressler, J., Chen, B. H., Ligthart, S., Guarrera, S., Colicino, E., Just, A. C., Wahl, S., Gieger, C., Vandiver, A. R., Tanaka, T., Hernandez, D. G., … Baccarelli, A. A. (2019). Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease. Circulation, 140(8), 645–657. https://doi.org/10.1161/CIRCULATIONAHA.118.039357

 

Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology38(1), 23–38. https://doi.org/10.1038/npp.2012.112

 


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