loading page

Identification of MicroRNAs in Children with Increased Asthma Bronchodilator Usage in Genetics of Asthma in Costa Rica Study
  • +6
  • Richard Wong,
  • Brinda Desai,
  • Rinku Sharma,
  • Upasna Srivastava,
  • Alvin Kho T,
  • Scott T. Weiss,
  • Juan Celedon,
  • Michael McGeachie ,
  • Kelan Tantisira
Richard Wong
University of California San Diego

Corresponding Author:[email protected]

Author Profile
Brinda Desai
University of California San Diego
Author Profile
Rinku Sharma
Brigham and Women's Hospital Channing Division of Network Medicine
Author Profile
Upasna Srivastava
Yale University
Author Profile
Alvin Kho T
Brigham and Women's Hospital Channing Division of Network Medicine
Author Profile
Scott T. Weiss
Brigham and Women's Hospital Channing Division of Network Medicine
Author Profile
Juan Celedon
Children's Hospital of Pittsburgh of UPMC
Author Profile
Michael McGeachie
Brigham and Women's Hospital Channing Division of Network Medicine
Author Profile
Kelan Tantisira
University of California San Diego
Author Profile

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.
23 Mar 2024Submitted to Pediatric Pulmonology
15 Apr 2024Reviewer(s) Assigned
16 Jul 20241st Revision Received
16 Jul 2024Review(s) Completed, Editorial Evaluation Pending
16 Jul 2024Submission Checks Completed
16 Jul 2024Assigned to Editor
16 Jul 2024Reviewer(s) Assigned
19 Aug 2024Editorial Decision: Accept