Key result
Blood-based F2RL3 hypomethylation linked to ~32% higher CHD risk.
Why the study?
Although F2RL3 methylation has been linked to cardiovascular mortality in Caucasians, its diagnostic value for coronary heart disease and its association in the Chinese population were unknown.
Does blood-based F2RL3 methylation associate with the presence of coronary heart disease in a Chinese population?
Case-Control (n=364)
Does blood-based F2RL3 methylation associate with the presence of coronary heart disease in a Chinese population?
Blood-based F2RL3 hypomethylation is a potential biomarker for detecting coronary heart disease, particularly in older patients or those with myocardial infarction.
F2RL3 methylation may mark CHD risk in Chinese adults; extends Caucasian mortality data but leaves clinical utility open.
Background and Aims: Previous work has shown the association between blood-based methylation of coagulation factor II receptor-like 3 gene (F2RL3) and cardiovascular mortality in Caucasians. However, the diagnostic value of F2RL3 methylation for CHD is still unknown. The aim of our study was to evaluate the association between blood-based F2RL3 methylation and the risk of CHD in the Chinese population. Methods: The methylation level of F2RL3 was quantified by mass spectrometry in a case-control study with 180 CHD cases and 184 controls. The association between F2RL3 methylation intensity and CHD was assessed by logistic regression models, controlling confounding factors. Results: The hypomethylation in F2RL3_A amplicon was significantly associated with CHD (odds ratio (ORs) per -10% methylation: 1.22–1.42, p < 0.035 for six out of seven CpG loci). Specifically, this significant association was observed in elderly CHD patients (≥60 years), myocardial infarction (MI) patients, heart failure patients and the patients with minor to medium cardiac function impairment (NYHA Ⅰ&Ⅱ CHD cases) (ORs per -10% methylation: 1.35–1.58, 1.32–2.00, 1.29–1.43, 1.25–1.44; p < 0.024, 0.033, 0.035, 0.025, respectively). However, F2RL3_B CpG sites showed no or very weak association with CHD. The combination of F2RL3_A_CpG_1 and F2RL3_A_CpG_3 methylation levels could efficiently discriminate CHD, MI, heart failure, NYHA I&II CHD, and elderly CHD patients from controls (area under curve (AUC) = 0.75, 0.79, 0.75, 0.76, and 0.82, respectively). Conclusion: We propose blood-based F2RL3 methylation as a potential biomarker for CHD, especially for people with older age or with the status of MI. The combination of F2RL3 methylation and conventional risk factors might be an approach to evaluate CHD at early stage.
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Zhao et al. (2022) conducted a case-control in Coronary Heart Disease (n=364). F2RL3 hypomethylation vs. Controls was evaluated on Coronary Heart Disease (OR 1.22-1.42, p=<0.035). Blood-based hypomethylation in the F2RL3_A amplicon was significantly associated with coronary heart disease (OR per -10% methylation: 1.22-1.42, p<0.035).
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