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瓣膜性心房颤动中的DNA甲基化失调

DNA methylation dysregulations in valvular atrial fibrillation.

作者信息

Shen Kangjun, Tu Tao, Yuan Zhaoshun, Yi Jiangfeng, Zhou Yangzhao, Liao Xiaobo, Liu Qiming, Zhou Xinmin

机构信息

Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

出版信息

Clin Cardiol. 2017 Sep;40(9):686-691. doi: 10.1002/clc.22715. Epub 2017 Aug 28.

Abstract

BACKGROUND

The epigenetic changes underlying the development of atrial fibrillation (AF) remain incompletely understood. Limited evidence suggests that abnormal DNA methylation might be involved in the pathogenesis of AF. In the present study, we evaluated the methylation status of genomic DNA from myocardial tissue in AF patients and sinus rhythm (SR) patients systematically.

HYPOTHESIS

DNA methylation dysregulations will be associated with valvular AF.

METHODS

Right atrial myocardial tissue was obtained from rheumatic valvular patients who had undergone valve replacement surgery (SR group, n = 10; AF group, n = 10). The global DNA methylation level, the promoter methylation level of the natriuretic peptide receptor-A gene (NPRA), and its correlation with the mRNA expression level of DNA methyltransferase genes were detected.

RESULTS

The global DNA methylation level was significantly higher in the AF group than in the SR group (P < 0.05). The NPRA mRNA expression was decreased and the NPRA gene was hypermethylated in the AF group (P < 0.05). Meanwhile, the NPRA mRNA expression level has a negative correlation with the mean methylation level in the promoter region of the NPRA gene.

CONCLUSIONS

DNA methylation dysregulations may be relevant in the pathogenesis of AF. DNA methyltransferase 3B likely plays an essential role in the DNA methylation dysregulations in AF.

摘要

背景

心房颤动(AF)发生发展过程中的表观遗传变化仍未完全明确。有限的证据表明,异常的DNA甲基化可能参与AF的发病机制。在本研究中,我们系统评估了AF患者和窦性心律(SR)患者心肌组织基因组DNA的甲基化状态。

假设

DNA甲基化失调将与瓣膜性AF相关。

方法

从接受瓣膜置换手术的风湿性瓣膜病患者获取右心房心肌组织(SR组,n = 10;AF组,n = 10)。检测总体DNA甲基化水平、利钠肽受体A基因(NPRA)的启动子甲基化水平及其与DNA甲基转移酶基因mRNA表达水平的相关性。

结果

AF组的总体DNA甲基化水平显著高于SR组(P < 0.05)。AF组中NPRA mRNA表达降低且NPRA基因高度甲基化(P < 0.05)。同时,NPRA mRNA表达水平与NPRA基因启动子区域的平均甲基化水平呈负相关。

结论

DNA甲基化失调可能与AF的发病机制相关。DNA甲基转移酶3B可能在AF的DNA甲基化失调中起重要作用。

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DNA methylation dysregulations in valvular atrial fibrillation.瓣膜性心房颤动中的DNA甲基化失调
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本文引用的文献

1
Level Of Natriuretic Peptide Determines Outcome In Atrial Fibrillation.利钠肽水平决定房颤的预后。
J Atr Fibrillation. 2010 Jan 1;2(4):227. doi: 10.4022/jafib.227. eCollection 2010 Jan-Feb.
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Epigenetic regulation in heart failure.心力衰竭中的表观遗传调控。
Curr Opin Cardiol. 2016 May;31(3):255-65. doi: 10.1097/HCO.0000000000000276.
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Aberrant DNA methylation in the pathogenesis of atherosclerosis.动脉粥样硬化发病机制中的异常 DNA 甲基化。
Clin Chim Acta. 2016 May 1;456:69-74. doi: 10.1016/j.cca.2016.02.026. Epub 2016 Mar 2.

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