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The association between ACTB methylation in peripheral blood and coronary heart disease in a case-control study
Jialie Jin1, Chao Zhu2, Jinxin Wang3
1Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Insights
Blood-based hypermethylation of beta-actin (ACTB) is linked to increased coronary heart disease (CHD) risk, particularly in men and heart failure patients. This finding offers a new approach for CHD risk assessment.
Area of Science:
- Biomarkers and epigenetics in cardiovascular disease research.
- Molecular mechanisms underlying coronary heart disease (CHD) pathogenesis.
Background:
- Coronary heart disease (CHD) poses a significant global health burden, necessitating innovative and minimally invasive risk assessment tools.
- Previous research indicated a link between hypomethylation of beta-actin (ACTB) and stroke risk, but its association with CHD remained unexplored.
Purpose of the Study:
- To investigate the association between blood-based ACTB methylation patterns and the risk of developing CHD.
- To evaluate ACTB methylation as a potential biomarker for CHD risk stratification in the Chinese population.
Main Methods:
- A case-control study involving 281 CHD patients and 272 controls.
- Quantitative determination of ACTB methylation levels using mass spectrometry.
- Logistic regression analysis was employed to assess the association between ACTB methylation and CHD risk, adjusting for confounding factors.
Main Results:
- Significant association found between ACTB hypermethylation in peripheral blood and increased CHD risk (ORs per +10% methylation: 1.19-1.45, p < 0.013).
- The association was particularly pronounced in male subjects and patients with heart failure (HF).
- Specific CpG sites (ACTB_CpG_2.3, ACTB_CpG_7.8, ACTB_CpG_9.10) hypermethylation correlated with CHD risk and could discriminate CHD cases, especially those with mild to moderate cardiac impairment (NYHA I&II).
Conclusions:
- Blood-based ACTB hypermethylation is strongly associated with an elevated risk of coronary heart disease.
- Combining ACTB methylation analysis with conventional risk factors may offer a novel strategy for enhancing CHD risk assessment.
- The findings highlight the potential of ACTB methylation as a predictive biomarker for CHD.
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.
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