Role of DNA Methylation in Development of Cardiovascular Diseases, Resulting in a Sudden Cardiac Death (Review)

Abstract

An effective system to diagnose predisposition to development of sudden cardiac death (SCD) is required in order to determine the risk of developing a sudden fatal outcome well in advance of the onset thereof, including in people with asymptomatic cardiovascular disease, as well as to implement early preventive measures that can result in a decrease in the population mortality from cardiovascular diseases. Thus, the search for SCD risk markers becomes a topical issue for modern health care. According to recent studies, epigenetic mechanisms of heredity, and DNA methylation above all, play an important role in development of many diseases. The review provides the results of recent foreign and Russian studies on identification of a link between DNA methylation and development of cardiovascular diseases being the basis for SCD (IHD, cardiomyopathies, heart rhythm disturbances). The major part of the review is dedicated to studying DNA methylation in IHD, which is the most epigenetically explored nosology at the moment. Attention is also paid to studies of the DNA methylation role in development of acute coronary syndrome and myocardial infarction, which have development mechanisms similar to those of SCD. There were only few studies on identification of a link between DNA methylation and cardiomyopathies and cardiac arrhythmias conducted, however, an association of specific genes methylation with the explored nosologies was revealed. The review also provides pathogenetic substantiations of the possibilities to use epigenetic markers of cardiovascular diseases as SCD markers. Thus, it has been established that study of genes the methylation of which is associated with IHD ( CTH , PLCB1 , PTX3 , MMP9 , FN1 , F2RL3 , ABCB1 , FOXP3 , GDF15 , IL6 , CASR ), with lipid metabolism disorders and atherosclerosis ( CETP , CCL2 , SREBF2 , TIMP1 ), as well as with heart rhythm disturbances ( SCN5A and KCNQ1 ), may be most promising in relation to SCD.