循环微小RNA-204水平与糖尿病人群冠状动脉钙化相关性分析  

Correlation between circulating microRNA-204 level and coronary artery calcification in patients with diabetes

作　　者：裴昱强 丁耀东 王睿 梁静[1] 刘晓丽[1] 申华[1] 葛海龙[1] PEI Yuqiang;DING Yaodong;WANG Rui;LIANG Jing;LIU Xiaoli;SHEN Hua;GE Hailong(Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院心内科,北京市100029

出　　处：《中国动脉硬化杂志》2020年第7期578-583,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81573744,81973841)。

摘　　要：目的探讨糖尿病患者血浆循环微小RNA-204(microRNA-204)水平与冠状动脉CT血管成像(CCTA)钙化积分(CACS)的相关性。方法横断面分析2017年1月至2018年12月在首都医科大学附属北京安贞医院确诊并行冠状动脉CTA的糖尿病患者179例,经CACS评估冠状动脉钙化(CAC)的严重程度,将患者分为冠状动脉钙化组(CACS>10,99例)及非钙化组(CACS≤10,80例)。从中选取匹配的5例钙化组(CACS>10)和5例非钙化组(CACS≤10)的患者,使用microRNA微阵列分析其血浆microRNA水平。为了验证微阵列分析的结果,使用qRT-PCR对两组microRNA-204定量检测,进行单变量线性回归评估microRNA-204水平与CACS之间的潜在相关性。通过ROC曲线分析,评估microRNA-204的潜在诊断能力。结果两组患者在空腹血糖(FPG)、糖化血红蛋白(HbA1c)方面比较,差异有统计学意义(P<0.05)。microRNA微阵列分析得到钙化组较非钙化组microRNA-204表达水平显著下降。经qRT-PCR进一步印证了钙化组血浆中microRNA-204显著下调(P<0.05)。通过单变量线性回归分析显示,钙化组血浆循环microRNA-204水平与反应冠状动脉钙化严重程度的CACS呈负相关。ROC曲线显示,microRNA-204预测糖尿病患者发生冠状动脉钙化的曲线下面积为0.9487(0.9191~0.9782,P<0.0001),诊断临界值为21.3,敏感度为96.3%,特异度为79.6%。结论钙化组患者血浆中microRNA-204表达水平显著下降,而反映冠状动脉钙化严重程度的CACS与microRNA-204之间存在负相关,可能对进一步验证人血浆microRNA-204水平宏观反映糖尿病患者是否存在冠状动脉钙化有重要意义。microRNA-204可能是诊断冠状动脉钙化的新型生物标志物。Aim To investigate the correlation between circulating microRNA-204 levels and coronary CT angiography(CTA)calcification score(CACS)in patients with diabetes.Methods Clinical data from 179 patients diagnosed with diabetes who underwent coronary CT angiography in our hospital from January 2017 to December 2018,were cross-section analyzed.Patients were divided into moderate to severe calcification group(CACS>10,99 cases)and non-or minimal calcification group(CACS≤10,80 cases).Five patients with coronary artery calcification(CAC)(CACS>10)and 5 patients with non-CAC(CACS≤10)were selected for microRNA microarray analysis of plasma microRNAs.Two groups of microRNA-204 were quantified by using qRT-PCR and univariate linear regression was performed to assess the potential correlation between microRNA-204 levels and CACS.The potential diagnostic ability of microRNA-204 was assessed by ROC curve analysis.Results There was significant difference in fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1 c)between two groups(P<0.05).MicroRNA microarray analysis showed a significant decrease in microRNA-204 expression levels in the CAC group compared with the non-CAC group.MicroRNA-204 was significantly down-regulated in the moderate-to-severe calcification group by qRT-PCR(P<0.05).Univariate linear regression analysis showed that circulating microRNA-204 levels in moderate to severe calcification group were negatively correlated with CACS,which reflected the severity of coronary artery calcification.The ROC curve showed that the area under the curve of microRNA-204 levels predicting vascular calcification of patients with diabetes was 0.9487(0.9191~0.9782,P<0.0001)and the diagnostic threshold was 21.3,the sensitivity was 96.3%,the specificity was 79.6%.Conclusion The expression level of microRNA-204 in plasma of CAC patients decreased significantly,but there was a negative correlation between the severity of CAC and microRNA-204,which may be of great significance to further verify that the level of microRNA-204 in human

关 键 词：微小RNA-204 冠状动脉钙化 糖尿病 糖化血红蛋白 

分 类 号：R5[医药卫生—内科学]