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

Abstract

BackgroundCirculating 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.MethodsWe 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.ResultsThe 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.ConclusionsCirculating 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.

MiR-206-3p alleviates chronic constriction injury-induced neuropathic pain through targeting HDAC4

“…MiRNAs are involved in multiple biological processes including cell proliferation, differentiation, and metabolism [13, 19, 29] by modulating specific genes. It has been shown that miRNAs are abnormally expressed in many types of diseases, including heart disease, inflammatory diseases, and especially cancers [20, 21, 30].…”

The Relationship Between MicroRNAs And Congenital Kidney Anomalies

“…Recently, it has been reported that some miRNAs are correlated with fetal heart diseases. This was determined using peripheral blood samples of pregnant women and these miRNAs were reported to originate in the placenta [24][25][26][27] . In light of this information we believe that specific miRNAs found in the cord blood of fetuses can be used as biomarkers for the antenatal early diagnosis of fetal kidney anomalies.…”

MicroRNA profiling of patients with sporadic atrial septal defect

“…There is a paucity of research on miRNA expression profiles in ASD. Song et al [39] reported that hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in the plasma of children with ASD. A miRNA SNP study indicated that the miR-196a2 (rs11614913 T > C) homozygous CC variant and the C allele are negatively associated with ASD [40].…”