The association between ACTB 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 (ACTB) was associated with increased risk of stroke, but not reported in CHD yet. OBJECTIVES: We aimed to explore the association between blood-based ACTB methylation and the risk of CHD in a case-control study in the Chinese population. METHODS: The methylation level of ACTB was quantitatively determined by mass spectrometry in 281 CHD patients and 272 controls. The association between ACTB methylation and CHD risk was estimated by logistic regression analyses adjusted for possible confounding effects. RESULTS: We found a significant association between hypermethylation of ACTB in peripheral blood and increased risk of CHD (odds ratios (ORs) per +10% methylation: 1.19–1.45, p < 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; p < 0.030, 1.52 × 10(−4), 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; p < 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 ACTB hypermethylation and CHD risk. The combination of ACTB methylation and conventional risk factors might provide a novel strategy to improve risk assessment of CHD.