MiR-125b的表达与传统危险因素对冠心病易感风险的交互作用研究

发布时间：2018-05-08 05:03

本文选题：冠心病 + microRNA　；参考：《南京医科大学》2017年硕士论文

【摘要】：目的:探索血浆microRNA的表达对于诊断冠心病和评估冠状动脉粥样硬化严重程度的潜在生物学标志物价值,并且探究microRNA的表达与传统危险因素对冠心病易感风险的交互作用。方法:本研究在2012至2013年期间,从中国伊犁哈萨克自治州友谊医院心内科住院治疗的患者中纳入共124例研究对象。冠状动脉造影确定66例冠心病病例组和58例非冠心病对照组,收集临床资料并且采集静脉血标本。采用实时定量PCR(qRT-PCR)技术测定文献已报道的与冠心病相关的20种microRNA的表达量。Gensini评分系统用以评判冠状动脉粥样硬化的严重程度。使用叉生分析法计算各因素的比值比以及microRNA与传统危险因素在冠心病易感风险方面的交互作用。结果:冠心病组中血浆miR-125b的表达低于非冠心病组(0.14±0.09、0.18±0.10,p=0.055),差异趋向有意义。两组间在年龄(p0.001)、男性性别(p=0.023)、高密度脂蛋白胆固醇(p=0.020)、血肌酐(p=0.033)、空腹血糖(p=0.006)、Gensini评分(p0.001)等传统危险因素方面差异具有统计学意义。并且随着Gensini评分的增加,血浆miR-125b的表达量显著降低(p=0.037)。此外,Spearman相关分析表明,Gensini评分与血浆miR-125b的表达呈负相关(r=-0.215,p=0.017)。受试者工作特征曲线显示,在所有入选的20种miRNAs中,miR-125b诊断冠心病的曲线下面积AUC最小(0.405;95%CI:0.305～0.506,p=0.070)。叉生分析结果显示miR-125b与冠心病传统危险因素之间存在交互作用。各自的交互作用指数为:年龄(SI=-50.99,SIM=5.48,AP=0.80);性别(SI=1.18,SIM=0.78,AP=0.12);CR(SI=1.46,SIM=1.00,AP=0.25);FBG(SI=1.25,SIM=0.77,AP=0.16);HDL-C(SI=1.50,SIM =0.92,AP=0.28)。值得注意的是miR-125b与年龄在冠心病交互作用的归因比高达80%。结论:与对照组相比,miR-125b在冠心病患者体内表达降低,并且随着Gensini评分的增加,其表达量明显减少。MiR-125b有望成为新的生物学标志物用于临床冠心病的诊断和冠状动脉粥样硬化严重程度的评估。此外,miR-125b与传统危险因素对冠心病的易感风险存在明确的交互作用,对临床早期筛选出更易罹患冠心病的高风险人群具有重要的意义。
[Abstract]:Objective: to explore the potential biomarker value of plasma microRNA expression in the diagnosis of coronary heart disease (CHD) and the severity of coronary atherosclerosis, and to explore the interaction between the expression of microRNA and traditional risk factors on the susceptibility to coronary heart disease (CHD). Methods: a total of 124 patients were enrolled in the study from 2012 to 2013 in the Department of Cardiology, Friendship Hospital of Yili Kazak Autonomous Prefecture, China. Coronary angiography confirmed 66 cases of coronary heart disease and 58 cases of non-coronary heart disease control group, collected clinical data and collected venous blood samples. The expression of 20 kinds of microRNA related to coronary artery disease (CHD) was measured by real-time quantitative PCRQ RT-PCR. Gensini scoring system was used to evaluate the severity of coronary atherosclerosis. The ratio ratio of each factor and the interaction between microRNA and traditional risk factors in the risk of coronary heart disease were calculated by using forked analysis method. Results: the expression of plasma miR-125b in coronary heart disease group was lower than that in non-coronary heart disease group (0.14 卤0.09) 0.18 卤0.10 p0. 055, and the difference tended to be significant. There were significant differences between the two groups in the traditional risk factors, such as age, male sex, high density lipoprotein cholesterol, serum creatinine, fasting blood glucose, and Gensini score (p 0.001), and there were significant differences between the two groups in the traditional risk factors, such as age, male sex, high density lipoprotein cholesterol, serum creatinine, and Gensini score (P 0.001). With the increase of Gensini score, the expression of plasma miR-125b decreased significantly. In addition, Spearman correlation analysis showed that there was a negative correlation between Gensini score and plasma miR-125b expression. The operating characteristic curve of the subjects showed that the area under the curve for diagnosing coronary heart disease (AUC) was 0.405% 95% CI: 0.305% 0.506% 0.506% and 0.070% under the curve for diagnosing coronary heart disease in all 20 kinds of miRNAs. Cross-birth analysis showed that there was interaction between miR-125b and traditional risk factors of coronary heart disease. Their interaction indexes were as follows: age sig 50.99 / SIMM 5.48 / 0.80; SIM-0.120.12. SIM1.00 / 0.25SIM0.77 / 0.16HDL-CIM0.50SIM 0.280.28. It is worth noting that the attribution ratio of the interaction between miR-125b and age in coronary heart disease is as high as 80. Conclusion: compared with the control group, the expression of miR-125b in patients with coronary heart disease decreased, and with the increase of Gensini score, The reduced expression of .MiR-125b is expected to be a new biomarker for the diagnosis of clinical coronary heart disease and the assessment of severity of coronary atherosclerosis. In addition, miR-125b has a clear interaction with traditional risk factors on the susceptibility to coronary heart disease, which is of great significance for screening the high-risk population with higher risk of coronary heart disease in the early clinical stage.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

【参考文献】