肥胖儿童循环miRNAs的差异表达研究及其与高血压的相关性研究

Differential Expression of Circulating miRNAs in Obese Children and Its Correlation with Hypertension

目的 探究肥胖儿童循环miRNAs的差异表达及其与成人高血压的相关性。方法 本研究招募的儿童和成人血清样本均来自作者医院。采用miRNA高通量测序来筛选肥胖儿童相关的循环miRNA。采用实时荧光逆转录定量聚合酶链反应(real-time reverse transcription quantitative polymerase chain reaction, RT-qPCR)验证从miRNA分析实验中鉴定的差异表达的候选miRNAs,并在患有高血压的成人中进一步研究靶向miRNAs的表达模式。采用受试者工作特征(receiver operating characteristic, ROC)曲线评估循环miR-486、miR-146b和miR-197预测成人高血压的价值。结果 与正常对照组比较,miR-222、miR-486、miR-146b、miR-146a、miR-15b在肥胖儿童中表达水平增加,miR-197在肥胖儿童中表达水平下降(P均<0.05)。此外,miR-222、miR-486、miR-146b、miR-146a和miR-15b与体质量指数(body mass index, BMI)呈正相关(P均<0.01),miR-197与BMI呈负相关(P<0.01)。与正常血压组相比,高血压组的miR-486、miR-146b相对血清水平显著增加(P均<0.05),miR-197相对血清水平显著降低(P<0.05)。miR-486、miR-146b分别与收缩压(r=0.351、0.542,P均<0.001)、舒张压(r=0.323、0.494,P均<0.001)呈正相关,miR-197与收缩压(r=-0.563,P<0.001)、舒张压(r=-0.544,P<0.001)呈负相关。ROC曲线分析结果显示,miR-486、miR-146b和miR-197能单独用于区分高血压患者和正常血压者(AUC=0.902、0.867、0.871,P均<0.001),3种miRNAs组合用于区分高血压患者和正常血压者具有最大预测价值(AUC=0.996,P<0.001)。结论 miR-486、miR-146b和miR-197有可能指示肥胖儿童在未来发展为高血压的风险。

Objective To explore the differential expression of circulating miRNAs in obese children and its correlation with adult hypertension. Methods This study recruited serum samples from children and adults in the author′s hospital. Circulating miRNAs related to obese children was screened by miRNA high-throughput sequencing. Real-time reverse transcription quantitative polymerase chain reaction(RT-qPCR) was used to verify the differentially expressed candidate miRNAs identified in the miRNA analysis experiment, and the expression patterns of targeted miRNAs were further studied in adults with hypertension. The value of circulating miR-486, miR-146b and miR-197 in predicting adult hypertension was evaluated by receiver operating characteristic(ROC) curve. Results Compared with the healthy control group, the expression level of miR-222, miR-486, miR-146b, miR-146a and miR-15b in obese children increased, and the expression level of miR-197 decreased(all P<0.05). In addition, miR-222, miR-486, miR-146b, miR-146a and miR-15b were positively correlated with body mass index(BMI)(all P<0.01), while miR-197 was negatively correlated with BMI(P<0.01). Compared with the normal blood pressure group, the relative serum levels of miR-486, miR-146b in hypertension group increased significantly(all P<0.05), while the relative serum level of miR-197 significantly decreased(P<0.05). miR-486 and miR-146b were positively correlated with systolic blood pressure(r=0.351,0.544, all P<0.001) and diastolic blood pressure(r=0.323, 0.494, all P<0.001), and miR-197 was negatively correlated with systolic blood pressure(r=-0.563, P<0.001) and diastolic blood pressure(r=-0.544,P<0.001). ROC curve analysis showed that miR-486, miR-146b and miR-197 could be used alone to distinguish hypertension patients and normotensive(AUC=0.902, 0.867 and 0.871, all P<0.001), and the combination of three miRNAs had the greatest predictive value for distinguishing hypertensive patient from normotensive(AUC=0.996, P<0.001). Conclusion miR-486, miR-146b and miR-197 may indicate the risk of obesity children developing hypertension in the future.