The Association Between DNA Methylation of 6p21.33 and AHRR in Blood and Coronary Heart Disease in Chinese Population

Background: Early detection could significantly improve the prognosis of coronary heart disease (CHD). In-invitro diagnostic technique may provide a solution when sufficient biomarkers could be identified. Pertinent associations between blood-based aberrant DNA methylation and smoking, the pathogenesis of atherosclerosis, and CHD have been robustly demonstrated and replicated, but that studies in Chinese populations are rare. The blood-based methylation of aryl-hydrocarbon receptor repressor (AHRR) cg05575921 and 6p21.33 cg06126421 has been associated with cardiovascular mortality in Caucasians. Here, we aim to investigate whether the AHRR and 6p21.33 methylation in the blood is associated with CHD in the Chinese population.Methods: In this case-control study,180 CHD patients and 184 controls were enrolled. Methylation intensities of 19 CpG sites, including AHRR cg05575921, 6p21.33 cg06126421, and their flanking CpG sites, were quantified by mass spectrometry. The association between methylation intensities and CHD was estimated by logistic regression analyses adjusted for covariant.Results: Compared to the controls, lower methylation of 6p21.33_CpG_4.5/cg06126421 was independently associated with increased odds of CHD patients with heart failure and early cardiac dysfunction (OR per -10% methylation = 1.59 and 1.65; p = 0.012 and 0.020 by multiple testing corrections, respectively). No association between blood-based AHRR methylation and CHD was found.Conclusions: 6p21.33 methylation exhibits a significant association with CHD. The combination of 6p21.33 methylation and conventional risk factors might be an intermediate step towards the early detection of CHD.