DNA methylation and hydroxymethylation are associated with the degree of coronary atherosclerosis in elderly patients with coronary heart disease

Aims: DNA methylation and hydroxymethylation are significantly related to the occurrence and development of coronary heart disease (CHD) and atherosclerosis (AS). 5-Methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) are used to assess DNA methylation and hydroxymethylation levels, respectively. However, 5-mC and 5-hmC levels associated with CHD remain controversial. In the present study, we aimed to investigate the association of the peripheral blood levels of 5-mC and 5-hmC and the degree of coronary atherosclerosis in elderly CHD patients. Main methods: 5-mC and 5-hmC levels in peripheral blood mononuclear cells (PBMCs) were measured in 44 CHD patients and 42 matched control subjects by ELISA and dot blot analysis. Immunohistochemical staining was used to observe 5-mC, 5-hmC and TET2 expression in human aortic tissue. Gensini score was used to evaluate the degree of coronary atherosclerosis. Key findings: 5-mC and 5-hmC levels in PBMCs from CHD patients and in human aortic atherosclerosis plaque were both higher than those in control subjects and in tissue samples. TET2 expression was significantly upregulated in CHD patients compared with control subjects, while only an increasing trend in the expression of DNMT1, DNMT3A and all the other TET genes were found. Spearman correlation analysis demonstrated that 5-mC and 5-hmC levels were positively correlated with Gensini score. 5-mC and 5-hmC were considered as the risk factors for CHD after adjustment. Significance: DNA methylation and hydroxymethylation levels in PBMCs from elderly CHD patients were significantly increased, showing a positive correlation with the degree of coronary atherosclerosis.