Identification of MicroRNAs in Children with Increased Asthma
Bronchodilator Usage in Genetics of Asthma in Costa Rica Study
Abstract
Introduction: Uncontrolled or severe asthma results in symptomatic usage
of short-acting ß2-agonist usage (SABA). MicroRNAs (miRNAs) are
post-translational regulators that can influence asthma biology. This
study aims to identify miRNAs that are associated with increased SABA
usage. Methods: Small RNA sequenced from blood serum of 1,132 asthmatic
children aged 6 to 14 years in the Genetics of Asthma in Costa Rica
Study (GACRS) was used for this analysis. Logistic regression identified
miRNAs in patients who required increased SABA usage. These miRNA were
validated for association with SABA induced BDR. Gene target pathway
analysis was performed on validated miRNAs. Results: 21 miRNAs were
significantly associated with increased SABA usage with OR ranging from
0.87 to 1.23. Two miRNAs, miR-378a-3p and miR-144-3p, had odds ratio
1.14 (1 - 1.29, p=0.05) and 1.11 (1.01-1.22, p = 0.035), respectively
for increased SABA usage and were also significantly associated with
bronchodilator response. Furthermore, a linear regression analysis
involving these miRNA and bronchodilator response revealed that
increased miR-378a-3p correlated with decreased BDR and increased
expression of miR-144-3p correlated with improving pulmonary function
with bronchodilators. In gene target KEGG pathway analysis, the
erythroblastosis viral oncogene (ErbB) signaling pathway had among one
of the highest fold enrichment and p-value. Conclusion: Increased
expression miR-378a-3p and miR-144-3p was seen in this patient
population who required increased SABA usage. There were different
bronchodilatory effects seen in these two miRNAs, suggesting different
potential mechanisms underlying increased SABA usage.