The association between methylation in peripheral blood and coronary heart disease in a case-control study.

BACKGROUND

Coronary heart disease (CHD) brings a heavy burden to society worldwide. Novel and minimally invasive biomarkers for the risk evaluation of CHD are urgently needed. Previous study has revealed that blood-based hypomethylation of β-actin () was associated with increased risk of stroke, but not reported in CHD yet.

OBJECTIVES

We aimed to explore the association between blood-based methylation and the risk of CHD in a case-control study in the Chinese population.

METHODS

The methylation level of was quantitatively determined by mass spectrometry in 281 CHD patients and 272 controls. The association between methylation and CHD risk was estimated by logistic regression analyses adjusted for possible confounding effects.

RESULTS

We found a significant association between hypermethylation of in peripheral blood and increased risk of CHD (odds ratios (ORs) per +10% methylation: 1.19-1.45, < 0.013 for nine out of thirteen CpG sites), especially in male subjects and heart failure (HF) patients (ORs per +10% methylation: 1.20-1.43, 1.38-1.46; < 0.030, 1.52 × 10, respectively). Hypermethylation of ACTB_CpG_2.3, ACTB_CpG_7.8, and ACTB_CpG_9.10 was observed in the CHD patients with minor to medium cardiac function impairment (NYHA I&II CHD cases) (ORs per +10% methylation: 1.38-1.44; < 0.001). The combination of ACTB_CpG_2.3, ACTB_CpG_7.8, and ACTB_CpG_9.10 methylation levels could efficiently discriminate CHD cases, male CHD patients, HF and NYHA I&II CHD patients from controls (area under curve (AUC) = 0.75, 0.74, 0.73, and 0.77, respectively).

CONCLUSIONS

Our study reveals a strong association between blood-based hypermethylation and CHD risk. The combination of methylation and conventional risk factors might provide a novel strategy to improve risk assessment of CHD.