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

    Access Status
    Fulltext not available
    Authors
    Song, Y.
    Higgins, H.
    Guo, J.
    Harrison, K.
    Schultz, E.
    Hales, B.
    Moses, E.
    Goldblatt, J.
    Pachter, N.
    Zhang, Guicheng
    Date
    2018
    Type
    Journal Article
    
    Metadata
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    Citation
    Song, Y. and Higgins, H. and Guo, J. and Harrison, K. and Schultz, E. and Hales, B. and Moses, E. et al. 2018. Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children. Journal of Translational Medicine. 16 (1).
    Source Title
    Journal of Translational Medicine
    DOI
    10.1186/s12967-018-1411-0
    ISSN
    1479-5876
    School
    School of Public Health
    URI
    http://hdl.handle.net/20.500.11937/68011
    Collection
    • Curtin Research Publications
    Abstract

    © 2018 The Author(s). 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.

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