Exploring potential associations between low-dose cardiac catheterization radiation and blood microRNA changes in children with congenital heart disease.

The risk of cancer from medical exposure to ionizing radiation (IR) in pediatric patients-particularly those with congenital heart disease (CHD)-is a concern, given the need for repeated X-ray-guided cardiac catheterization (CC) procedures throughout their lives. To better understand the effects of low-dose IR, this study-part of the European HARMONIC project-investigated changes in blood miRNA expression following CC in CHD patients. Small RNA sequencing was performed on a discovery cohort of 10 CHD patients at three time points: before CC (T0), immediately after (T1), and 1 year later (T2). Differentially expressed miRNAs were validated in an independent group of 15 patients using quantitative real-time polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes pathway annotation analysis was carried out to determine the biological pathways involving target genes regulated by the dysregulated miRNAs. At the discovery stage, 74 miRNAs were significantly differentially expressed between the T1 and T0 groups, 69 between the T2 and T0 groups, and 41 between the T2 and T1 groups (q-value < 0.05 and |log2(fold change)|>1). Sixteen miRNAs (9 upregulated and 7 downregulated) were found to be dysregulated in both T1 and T2 compared to T0. Additionally, seven known miRNAs were uniquely dysregulated at T2. qRT-PCR analysis of six selected miRNAs partially validated the sequencing results, confirming consistent expression patterns for four miRNAs across cohorts. Pathway enrichment analysis indicated that predicted miRNA target genes were overrepresented in several pathways, including those annotated as cancer-related (enrichment P < .0001). These findings suggest potential associations with radiation exposure, but their biological significance and health implications remain uncertain and require further investigation.