AUTHOR=Jin Jialie , Zhu Chao , Wang Jinxin , Zhao Xiaojing , Yang Rongxi 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.972566

DOI=10.3389/fcvm.2022.972566

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>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 (<italic>ACTB</italic>) was associated with increased risk of stroke, but not reported in CHD yet.</p></sec><sec><title>Objectives</title><p>We aimed to explore the association between blood-based <italic>ACTB</italic> methylation and the risk of CHD in a case-control study in the Chinese population.</p></sec><sec><title>Methods</title><p>The methylation level of <italic>ACTB</italic> was quantitatively determined by mass spectrometry in 281 CHD patients and 272 controls. The association between <italic>ACTB</italic> methylation and CHD risk was estimated by logistic regression analyses adjusted for possible confounding effects.</p></sec><sec><title>Results</title><p>We found a significant association between hypermethylation of <italic>ACTB</italic> in peripheral blood and increased risk of CHD (odds ratios (ORs) per +10% methylation: 1.19–1.45, <italic>p</italic> &lt; 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; <italic>p</italic> &lt; 0.030, 1.52 × 10<sup>−4</sup>, 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&amp;II CHD cases) (ORs per +10% methylation: 1.38–1.44; <italic>p</italic> &lt; 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&amp;II CHD patients from controls (area under curve (AUC) = 0.75, 0.74, 0.73, and 0.77, respectively).</p></sec><sec><title>Conclusions</title><p>Our study reveals a strong association between blood-based <italic>ACTB</italic> hypermethylation and CHD risk. The combination of <italic>ACTB</italic> methylation and conventional risk factors might provide a novel strategy to improve risk assessment of CHD.</p></sec>