背景和目的:先前的研究表明,高加索人群中凝血因子II受体样3基因(F2RL3)的血液甲基化与心血管死亡率之间存在关联。然而,F2RL3甲基化对CHD的诊断价值尚不清楚.我们研究的目的是评估中国人群中基于血液的F2RL3甲基化与冠心病风险之间的关系。方法:在180例CHD病例和184例对照的病例对照研究中,通过质谱法定量F2RL3的甲基化水平。F2RL3甲基化强度与CHD之间的关联通过logistic回归模型进行评估。控制混杂因素。结果:F2RL3_A扩增子的低甲基化与CHD显着相关(每-10%甲基化的比值比(ORs):1.22-1.42,7个CpG基因座中的6个p<0.035)。具体来说,在老年冠心病患者(≥60岁)中观察到这种显著的相关性,心肌梗死(MI)患者,心力衰竭患者和轻度至中度心功能损害患者(NYHAⅠ和ⅡCHD病例)(ORs/-10%甲基化:1.35-1.58、1.32-2.00、1.29-1.43、1.25-1.44;p分别<0.024、0.033、0.035、0.025)。然而,F2RL3_BCpG位点显示与CHD没有或非常弱的关联。F2RL3_A_CpG_1和F2RL3_A_CpG_3甲基化水平的组合可以有效区分CHD,MI,心力衰竭,NYHAI&IICHD,和对照组的老年CHD患者(曲线下面积(AUC)分别=0.75、0.79、0.75、0.76和0.82)。结论:我们提出基于血液的F2RL3甲基化作为CHD的潜在生物标志物,特别是对于年龄较大或患有MI的人。F2RL3甲基化和常规危险因素的结合可能是早期评估CHD的一种方法。
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.