Early life microRNA programming of asthma and allergic diseases

Rationale: microRNAs (miRNAs) are involved in the biological regulation of asthma and allergies. We hypothesize that miRNAs from cord blood at birth can predict early childhood asthma and allergic diseases.

Methods: Paired miRNA and messenger RNA (mRNA) sequencing from cord blood was performed in subjects from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Multivariable miRNA differential expression analysis was performed to examine the association with doctor diagnosed asthma/recurrent wheeze, atopic dermatitis, food allergies, and allergic rhinitis at ages 3 and 6 years with FDR correction. Differentially expressed miRNAs were annotated to mRNA targets using miRTarBase and inversely correlated with target mRNA expression levels.

Results: In 389 subjects who were 46% female, 42% White, and 40% Black, two cord blood miRNAs, miR-200c (q=1.43×10-4) and miR-23b (q=1.74×10-2), were associated with age 3 recurrent wheeze and target gene expression, including GGPS1–a regulator of lipid synthesis induced by IL-4 and IL-6. Twenty miRNAs, including miR-193b (q=3.05×10-5), miR-145 (q=2.96×10-4), and miR-221 (q=1.62×10-3), were associated with age 6 asthma and target gene expression. Cord blood miRNAs were also predictive of the longitudinal development of transient wheeze at age 3 years and persistent wheeze at age 6 years, in addition to atopic dermatitis and allergic rhinitis at ages 3 and 6 years.

Conclusions: The epigenetic miRNA programming of early childhood asthma and allergic diseases is present at birth, including the differential expression of miRNAs that regulate IL-33 (miR-200c), type 2 inflammation (miR-23b), lung function (miR-145), and airway remodeling (miR-221), and these miRNAs may serve as potential biomarkers and therapeutic targets.