Early-life microRNA signatures in cord blood associated with allergic rhinitis and asthma development

Abstract

Background

MicroRNAs (miRNAs) are involved in the biological regulation of asthma and allergies.

Objective

We sought to investigate the association between cord blood miRNAs and the development of allergic rhinitis and early childhood asthma.

Methods

miRNAs were sequenced from cord blood of subjects participating in the Vitamin D Antenatal Asthma Reduction Trial. Multivariable miRNA differential expression analyses were performed to examine their association with physician-diagnosed asthma and allergic rhinitis by age 3 years as well as active asthma status at age 6 years. miRNA signatures were further investigated for their ability to induce human airway smooth muscle cell proliferation in vitro.

Results

In a cohort of 389 subjects, elevated cord blood expression of miR-149-5p was associated with both allergic rhinitis and asthma at age 3 years (log₂ fold change [log₂FC], 1.87 and 1.42, respectively; false-discovery rate [FDR] < 0.001) as well as active asthma status at age 6 years (log₂FC, 2.26; FDR < 0.001). Higher expressions of miR-99b-5p, miR-125a-5p, and miR-200c-3p were also associated with both diagnosis of allergic rhinitis at age 3 years and active asthma status at age 6 years (allergic rhinitis: log₂FC, 0.6, 0.62, and 1.06, respectively; FDR < 0.001; active asthma: log₂FC, 0.55, 0.60, and 1.10, respectively; FDR < 0.001). Higher expression of miR-145-5p was associated with both new-onset asthma after age 3 years and active asthma status at age 6 years (log₂FC, 0.73 and 0.40, respectively; FDR < 0.001). These 5 miRNA signatures target key hubs in the interactome module of 71 genes associated with allergic rhinitis and asthma. Transfection of miR-125a-5p and miR-145-5p into human airway smooth muscle cells induced cell proliferation.

Conclusions

The dysregulation of cord blood miRNAs at birth is associated with allergic rhinitis and early childhood asthma. The miRNAs that regulate postembryonic development and immune response may serve as potential biomarkers and preventive targets for asthma.