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血液中 6p21.33 区域的 DNA 甲基化与 AHRR 同中国人群冠心病的关联性。

The association between DNA methylation of 6p21.33 and AHRR in blood and coronary heart disease in Chinese population.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, West District, Beijing, 100050, China.

出版信息

BMC Cardiovasc Disord. 2022 Aug 13;22(1):370. doi: 10.1186/s12872-022-02766-8.

Abstract

BACKGROUND

Early detection could significantly improve the prognosis of coronary heart disease (CHD). In-invitro diagnostic technique may provide a solution when sufficient biomarkers could be identified. Pertinent associations between blood-based aberrant DNA methylation and smoking, the pathogenesis of atherosclerosis, and CHD have been robustly demonstrated and replicated, but that studies in Chinese populations are rare. The blood-based methylation of aryl-hydrocarbon receptor repressor (AHRR) cg05575921 and 6p21.33 cg06126421 has been associated with cardiovascular mortality in Caucasians. Here, we aim to investigate whether the AHRR and 6p21.33 methylation in the blood is associated with CHD in the Chinese population.

METHODS

In this case-control study, 180 CHD patients recruited at their first registration in our study center, and 184 controls randomly selected from the people who participated in the annual health examination were enrolled. Methylation intensities of 19 CpG sites, including AHRR cg05575921, 6p21.33 cg06126421, and their flanking CpG sites, were quantified by mass spectrometry. The association between methylation intensities and CHD was estimated by logistic regression analyses adjusted for covariant.

RESULTS

Compared to the controls, lower methylation of 6p21.33_CpG_4.5/cg06126421 was independently associated with increased odds of being a CHD patient (OR per - 10% methylation = 1.42 after adjustment for age, gender, and batch effect; p = 0.032 by multiple testing corrections). No association between blood-based AHRR methylation and CHD was found.

CONCLUSIONS

6p21.33 methylation exhibits a significant association with CHD. The combination of 6p21.33 methylation and conventional risk factors might be an intermediate step towards the early detection of CHD.

摘要

背景

早期发现可以显著改善冠心病(CHD)的预后。当能够确定足够的生物标志物时,体内诊断技术可能提供一种解决方案。血液中异常 DNA 甲基化与吸烟、动脉粥样硬化发病机制和 CHD 之间的相关关系已得到强有力的证明和复制,但在中国人群中的研究很少。芳烃受体阻遏物(AHRR)cg05575921 和 6p21.33 cg06126421 的血液甲基化与白种人的心血管死亡率有关。在这里,我们旨在研究血液中的 AHRR 和 6p21.33 甲基化是否与中国人群中的 CHD 相关。

方法

在这项病例对照研究中,180 名 CHD 患者在我们的研究中心首次登记时被招募,184 名对照者随机从参加年度健康检查的人群中选择。通过质谱法定量测定 19 个 CpG 位点(包括 AHRR cg05575921、6p21.33 cg06126421 及其侧翼 CpG 位点)的甲基化强度。通过逻辑回归分析调整协变量来估计甲基化强度与 CHD 之间的关联。

结果

与对照组相比,6p21.33_CpG_4.5/cg06126421 的甲基化程度较低与 CHD 患者的患病几率增加独立相关(调整年龄、性别和批次效应后每 -10%甲基化的 OR = 1.42;多重检验校正后 p = 0.032)。未发现血液中 AHRR 甲基化与 CHD 之间存在关联。

结论

6p21.33 甲基化与 CHD 显著相关。6p21.33 甲基化与传统危险因素的结合可能是 CHD 早期检测的一个中间步骤。

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