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Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children

Citation

Song, Y and Higgins, H and Guo, J and Harrison, K and Schultz, EN and Hales, BJ and Moses, EK and Goldblatt, J and Pachter, N and Zhang, G, Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children, Journal of Translational Medicine, 16, (1) Article 42. ISSN 1479-5876 (2018) [Refereed Article]


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Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1186/s12967-018-1411-0

Abstract

Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD.

Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD.

Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring.

Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays.

Item Details

Item Type:Refereed Article
Keywords:diagnostic biomarkers, MicroRNA, congenital heart defects
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Cardiology (incl. Cardiovascular Diseases)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cardiovascular System and Diseases
UTAS Author:Song, Y (Dr Yong Song)
ID Code:135691
Year Published:2018
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-11-08
Last Modified:2019-12-12
Downloads:2 View Download Statistics

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