DNA hydroxymethylation combined with carotid plaques as a novel biomarker for coronary atherosclerosis

DNA羟甲基化与颈动脉斑块相结合作为冠状动脉粥样硬化的新型生物标志物

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作者:Dan Jiang #, Ying Wang #, Guanglei Chang, Qin Duan, Linna You, Min Sun, Chunxiao Hu, Lei Gao, Shiyong Wu, Hongmei Tao, Kai Lu, Dongying Zhang

Abstract

Little is known about the diagnostic value of DNA methylation and hydroxymethylation for coronary atherosclerosis. Carotid plaque is a common marker for coronary atherosclerosis. Our aim is to determine whether DNA methylation and hydroxymethylation combined with carotid plaques can be useful to the diagnosis of coronary atherosclerosis. The 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels from peripheral blood mononuclear cells (PBMCs) were measured in 113 enrolled patients. Crouse score and Gensini score were used to evaluate the severity of carotid and coronary atherosclerosis, respectively. With the increasing of severity of carotid plaque, a stepwise upward trend was observed in 5-mC and 5-hmC levels from PBMCs, which were significantly correlated with the risk factors, Crouse score and Gensini score. Crouse score and 5-hmC, not 5-mC, were the risk factors for coronary atherosclerosis after adjustment for the risk factors (the history of diabetes, FPG and HbA1c). Receiver operating characteristic (ROC) analysis indicated that 5-hmC combined with Crouse score was the diagnostic biomarker for coronary atherosclerosis, with the highest areas under the curve (AUC) for 0.980 (0.933-0.997), valuable sensitivity for 96.23% and specificity for 91.67%. These findings suggest 5-hmC level combined with Crouse score may provide the meaningful information for coronary atherosclerosis diagnosis.

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