Circulating MicroRNA: Incident Asthma Prediction and Vitamin D Effect Modification

Area of Science:

• Biomarkers
• Pediatric Respiratory Medicine
• Molecular Biology

Background:

• Recurrent wheezing in early childhood affects approximately 50% of children, with half developing asthma.
• MicroRNAs (miRNAs) are recognized as non-invasive biomarkers with prognostic value.
• The potential role of vitamin D in modifying asthma development is an area of ongoing research.

Purpose of the Study:

• To investigate if circulating microRNAs can predict incident asthma in children.
• To determine if vitamin D modifies the predictive capacity of microRNAs for asthma development.
• To identify specific microRNAs and their pathways associated with asthma incidence.

Main Methods:

• Analysis of plasma samples from 75 children with recurrent wheezing at age 3 from the VDAART cohort.
• Small RNA sequencing, normalization, and filtering of miRNA data.
• Logistic regression and meta-analysis to associate miRNAs with asthma status at ages 5 and 7, considering vitamin D levels, validated in the Project Viva cohort.

Main Results:

• While overall miRNA effects were weak, 38 miRNAs showed significant interaction with vitamin D, and 32 had a main effect in the high vitamin D group.
• Nine overlapped miRNAs were replicated across cohorts, with target genes enriched in asthma-related KEGG pathways.
• MicroRNA hsa-miR-574-5p demonstrated strong prognostic ability for incident asthma (AUROC 0.83).

Conclusions:

• Circulating microRNAs are promising biomarkers for predicting incident asthma.
• The prognostic utility of microRNAs for asthma is significantly influenced by vitamin D levels.
• Combined analysis of microRNAs and vitamin D offers improved asthma prediction in at-risk children.