APOE hypermethylation is significantly associated with coronary heart disease in males.

APOE is involved in exogenous and endogenous lipid metabolism and is a candidate gene for coronary heart disease (CHD). Using the SYBR-Green quantitative methylation-specific PCR method, we measured APOE methylation levels in 640 cases of CHD and 436 controls. Meanwhile, we used the Sequenom MassARRAY platform to genotype APOE rs7412 and rs7259620. In men, we found that CHD patients had significantly lower levels of APOE methylation than non-CHD controls (P = 0.044). In addition, rs7412-T and rs7259620-A were protective factors for CHD in males (rs7412-T: OR = 0.527, allele P = 0.004; rs7259620-A: OR = 0.743, allele P = 0.029). In the CHD group and the non-CHD control group, APOE methylation levels were inversely correlated with age (total patients: r = -0.015, P = 0.009, total controls: r = -0.185, P = 1E-04). In the female control group, the APOE methylation levels were inversely correlated with plasma APOA1 protein levels (female controls: r = -0.188, P = 0.008). In the total controls and female controls, APOE methylation levels were inversely correlated with plasma APOE protein levels (total controls: r = -0.110, P = 0.031, female controls: r = -0.188, P = 0.008). Our GDMR interaction analysis showed that there was an interaction between APOE methylation and rs7412 (P = 0.011). In addition, there was a significant interaction between APOE methylation, rs7259620, gender, smoking, LDL, TC, and APOE protein levels in the risk of CHD (P = 0.011). In summary, our research showed that the methylation of APOE was important for the risk of CHD in men.