Integration of gene expression and DNA methylation profiles provides a molecular subtype for risk assessment in atherosclerosis
Integration of gene expression and DNA methylation profiles provides a molecular subtype for risk assessment in atherosclerosis
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基因表达和 DNA 甲基化谱的整合为动脉粥样硬化风险评估提供了分子亚型
DOI：
10.3892/mmr.2016.5120
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发表时间：
2016-06-01
影响因子：
3.4
通讯作者：
Yu, Zheng
中科院分区：
文献类型：
--
作者：
Ma, Sheng-Chao;Zhang, Hui-Ping;Yu, Zheng
本研究的目的是确定一种检测早期动脉粥样硬化（AS）的有效方法，以及提供有用的DNA甲基化谱作为检测AS的生物标志物。共招募了300名个体（150名AS患者和150名健康受试者），在12个基因启动子位点使用巢式甲基化特异性聚合酶链反应在一个测试集进行外周血DNA甲基化分析。基于测试集，TIMP金属肽酶抑制剂1（TIMP 1）、ATP结合盒亚家族A成员1（ABCA 1）和乙酰辅酶A乙酰转移酶1（ACAT 1）的启动子甲基化被确定为候选生物标志物;证明了最高的灵敏度（88%）和特异性（90%）。作为早期AS检测候选物的生物标志物在独立验证组（n=100）中进行验证。在验证集中，TIMP 1、ABCA 1和ACAT 1甲基化的组合分别实现了88%、70%和79%的灵敏度、特异性和符合率值。在目前的初步研究中，AS相关基因的DNA甲基化模式被观察到在AS患者的外周血中显著改变。因此，AS特异性甲基化的三个基因面板（TIMP 1，ABCA 1和ACAT 1）可能作为一个有价值的生物标志物，为早期检测AS。
The aim of the present study was to identify an effective method for detecting early-phase atherosclerosis (AS), as well as to provide useful DNA methylation profiles to serve as biomarkers for the detection of AS. A total of 300 individuals (150 AS patients and 150 healthy subjects) were recruited for peripheral blood DNA methylation analyses at 12 gene promoter loci using nested methylation-specific polymerase chain reaction in a test set. Based on the test set, the promoter methylation of TIMP metallopeptidase inhibitor 1 (TIMP1), ATP binding cassette subfamily A member 1 (ABCA1), and acetyl-CoA acetyltransferase 1 (ACAT1) were determined to be candidate biomarkers; demonstrating the highest sensitivity (88%) and specificity (90%). The biomarkers that were candidates for early AS detection were validated in an independent validation set (n=100). In the validation set, the combination of TIMP1, ABCA1 and ACAT1 methylation achieved sensitivity, specificity and coincidence rate values of 88, 70 and 79%, respectively. In the current pilot study, the patterns of DNA methylation of AS-associated genes were observed to be significantly altered in the peripheral blood of AS patients. Thus, the AS-specific methylation of the three-gene panel (TIMP1, ABCA1, and ACAT1) may serve as a valuable biomarker for the early detection of AS.