title: Micro-RNAs Let7e and 126 in Plasma as Markers of Metabolic Dysfunction in 10 to 12 Years Old Children.
abstract: BACKGROUND
  Growing 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.
  
  
  OBJECTIVE
  We 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.
  
  
  METHODS
  Pediatric 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.
  
  
  RESULTS
  Regression 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 < 0.001) in the ROC analysis which were improved when miR-126 was included in the analysis (AUC 0.729; p < 0.001). 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Division of Obstetrics and Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Bernardo J
authors.initials: BJ
authors.lastname: Krause
authors.affiliation: Division of Obstetrics and Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ivo
authors.initials: I
authors.lastname: Carrasco-Wong
authors.affiliation: Department of Public Health, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Angélica
authors.initials: A
authors.lastname: Dominguez
authors.affiliation: Division of Pediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pilar
authors.initials: P
authors.lastname: Arnaiz
authors.affiliation: Division of Obstetrics and Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farías
authors.affiliation: Division of Pediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Salesa
authors.initials: S
authors.lastname: Barja
authors.affiliation: Department of Public Health, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Mardones
authors.affiliation: Division of Obstetrics and Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Pediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Paola
authors.initials: P
authors.lastname: Casanello
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002648:Child; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D035683:MicroRNAs / Q000097:blood*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference; D049629:Waist-Hip Ratio
chemical_list: D015415:Biomarkers; D007328:Insulin; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D014280:Triglycerides