Micro-RNAs Let7e and 126 in Plasma as Markers of Metabolic Dysfunction in 10 to 12 Years Old Children

BackgroundGrowing evidence shows that metabolic syndrome (MetS) is already starting in childhood however there is no consensus regarding how to diagnose this condition in pediatric population. Studies in adults show that altered levels of specific micro-RNAs are related with components of the MetS.ObjectiveWe determined the plasma levels of four MetS-associated micro-RNAs (miR-126, miR-132, mir-145 and Let-7e) in 10 to 12 years old children with or without MetS traits.DesignPediatric subjects were selected from a cohort of 3325 school-age children, and clustered by the absence (control, n = 30), or the presence of 1 (n = 50), 2 (n = 41) or 3 (n = 35) MetS traits according to Cook´s criteria. Micro-RNAs were isolated from plasma, and levels of miR-126, miR-132, miR-145 and Let-7e were determined by Taqman qPCR.ResultsRegression analysis of the different MetS traits regarding the different miRNAs analyzed showed that Let-7e presented a negative association with HDL-C levels, but a positive correlation with the number of MetS traits. Levels of miR-126 presented a positive correlation with waist circumference, waist to hip ratio, BMI, and plasma triglycerides and VLDL-C. Levels of miR-132 showed a positive correlation with waist to hip ratio. Plasma levels of Let-7e were increased (~3.4 fold) in subjects with 3 MetS traits, and showed significant AUC (0.681; 95%CI = [0.58, 0.78]; p In silico analysis of the interaction of proteins derived from mRNAs targeted by Let7 and miR-126 showed an important effect of both Let-7e and miR-126 regulating the insulin signaling pathway.ConclusionsThese results suggest that changes in the plasma levels of Let-7e and miR-126 could represent early markers of metabolic dysfunction in children with MetS traits.背景 越来越多的证据表明，代谢综合征（metabolic syndrome, MetS）已在儿童群体中起病，但目前针对儿科人群的代谢综合征诊断标准尚未达成共识。成人相关研究显示，特定微小核糖核酸（micro-RNA, miRNA）的水平异常与代谢综合征的各组分密切相关。 目的 本研究旨在检测伴或不伴代谢综合征表型的10至12岁儿童体内4种与代谢综合征相关的微小核糖核酸（miR-126、miR-132、miR-145及Let-7e）的血浆水平。 设计 研究对象从3325名学龄儿童队列中筛选得出，依据库克（Cook）标准，按照是否存在代谢综合征表型进行分组：对照组（无代谢综合征表型，n=30）、伴1种代谢综合征表型组（n=50）、伴2种代谢综合征表型组（n=41）及伴3种代谢综合征表型组（n=35）。从血浆中分离微小核糖核酸，采用Taqman定量聚合酶链反应（Taqman qPCR）检测miR-126、miR-132、miR-145及Let-7e的表达水平。 结果 针对4种目标微小核糖核酸与不同代谢综合征表型的回归分析显示，Let-7e与高密度脂蛋白胆固醇（HDL-C）水平呈负相关，而与代谢综合征表型数量呈正相关。miR-126水平与腰围、腰臀比、体质量指数（BMI）、血浆甘油三酯及极低密度脂蛋白胆固醇（VLDL-C）水平呈正相关。miR-132水平与腰臀比呈正相关。伴3种代谢综合征表型的受试者血浆Let-7e水平升高约3.4倍，且呈现出具有统计学意义的受试者工作特征曲线下面积（AUC=0.681；95%置信区间CI=[0.58, 0.78]；p）。计算机模拟分析（in silico）显示，Let-7与miR-126靶向的mRNA所编码蛋白的相互作用通路中，Let-7e与miR-126均对胰岛素信号通路具有显著调控作用。 结论 本研究结果提示，血浆Let-7e与miR-126水平的变化可作为伴代谢综合征表型儿童代谢功能异常的早期生物标志物。