DNA Methylation,Hydroxymethylation And Cytokines Are Associated With The Degree Of Coronary Atherosclerosis In Elderly Patients With Coronary Heart Disease

Objective: To investigate the association of the peripheral blood levels of DNA methylation(5-mC),hydroxymethylation(5-hmC),cytokines(IL-1β,IL-6,TNF-α)and the degree of coronary atherosclerosis in elderly patients with coronary heart disease(CHD).Methods: 5-mC and 5-hmC levels in peripheral blood mononuclear cells(PBMCs)and the plasma level of cytokines were measured in 44 CHD patients and 42 matched control subjects by ELISA and dot blot analysis.The relative mRNA expression of cytokines,DNMT and TET genes was detected by RT-PCR.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.Results: 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 nosignificant difference in the the expression of DNMT1,DNMT3 A 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-hmC is more closely related to Gensini score than 5-mC.5-mC and 5-hmC were considered as the risk factors for CHD after adjustment.Conclusion: DNA methylation,hydroxymethylation and cytokines levels from elderly CHD patients were significantly increased,showing a positive correlation with the degree of coronary atherosclerosis and revealing the potential diagnostic value as the biomarkers.