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. OBJECTIVES 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, 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 (HASMC) proliferation in vitro. RESULTS In a cohort of 389 subjects, elevated cord blood expression of miR-149-5p was associated with both age 3 allergic rhinitis and asthma (log2FC: 1.87 and 1.42, respectively, FDR<0.001), as well as age 6 active asthma status (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 of 3 years and active asthma status at age of 6 (allergic rhinitis: log2FC: 0.6, 0.62, and 1.06, respectively, FDR<0.001; active asthma: log2FC: 0.55, 0.60, 1.10, respectively, FDR<0.001, respectively). Higher expression of miR-145-5p was associated with both new onset asthma after age 3 and active asthma status at age 6 (log2FC: 0.73 and 0.40, FDR<0.001, respectively). These five 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 HASMC induced cell proliferation. CONCLUSION The dysregulation of cord blood miRNAs at birth are associated with allergic rhinitis and early childhood asthma. The miRNAs that regulate post-embryonic development and immune response may serve as potential biomarkers and preventive targets for asthma.