Circulating miRNAs and childhood asthma ICS response: a stratified analysis in the intervention arm of an RCT with vitamin D effect modification
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Le résumé fourni par la source
Background miRNAs play a crucial role in the anti-inflammatory effects of inhaled corticosteroids (ICS) in asthma. Vitamin D can modulate the expression of several miRNAs and reduces asthma exacerbations, but its molecular interaction with ICS remains unclear. Objective We hypothesised that vitamin D influences long-term ICS response through miRNA regulation. Methods Baseline serum miRNAs were sequenced from 462 subjects in the Childhood Asthma Management Program (CAMP), with 187 randomised to ICS treatment included in this study. Linear regression assessed associations between miRNA expression and prebronchodilator forced expiratory volume in 1 s per cent predicted (FEV 1 %) change over 4 years, stratified by baseline vitamin D levels and tested in interaction models. Microarray analysis of lymphoblastoid B cells (lymphoblastoid cell lines (LCLs)) from 22 CAMP subjects treated with dexamethasone (DEX), vitamin D or sham identified differentially expressed genes (DEGs). An miRNA target gene network was constructed, clustered and annotated by enrichment analysis. Top miRNAs were evaluated for ICS response prediction. Results 12 miRNAs were significantly associated with ICS-mediated FEV 1 % change in vitamin D insufficient subjects, and 11 miRNAs showed significant interaction with vitamin D (p≤0.05). Three miRNAs were approximately replicated in the Genetics of Asthma in Costa Rica Study. Microarray analysis identified 220 and 240 DEGs in DEX and vitamin D-treated LCLs, respectively. miRNAs hsa-miR-125a-5p, hsa-miR-181a-5p, hsa-miR-101-3p and hsa-miR-107 were enriched in haemopoiesis and leucocyte differentiation pathways (p≤0.05). Two miRNAs, hsa-miR-125a-5p and hsa-miR-181a-5p, predicted ICS response with an area under the receiver operating characteristic curve of 0.86 in the vitamin D insufficient group. Conclusions Vitamin D may modulate ICS response through miRNAs involved in immune cell differentiation, which could serve as biomarkers for ICS response, particularly in vitamin D insufficient individuals.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Circulating miRNAs and childhood asthma ICS response: a stratified analysis in the intervention arm of an RCT with vitamin D effect modification
- Date Crossref
- 04/06/2025
- Éditeur
- BMJ
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sun Yat-sen University Clinical Big Data Research Center pays non établi dans la noticeUniversité ou école supérieure
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The Seventh Affiliated Hospital of Sun Yat-sen University pays non établi dans la noticeÉtablissement de santé
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First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease pays non établi dans la noticeÉtablissement de santé
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State Key Laboratory of Respiratory Disease pays non établi dans la noticeStructure de recherche
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Guangzhou Institute of Respiratory Health pays non établi dans la noticeStructure de recherche
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Guangzhou Medical University pays non établi dans la noticeUniversité ou école supérieure
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Brigham and Women's Hospital Channing Division of Network Medicine pays non établi dans la noticeÉtablissement de santé
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Boston Children's Hospital Computational Health Informatics Program pays non établi dans la noticeÉtablissement de santé
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University of Pittsburgh Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Mass General Brigham pays non établi dans la noticeÉtablissement de santé
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University of California San Diego Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Partners Personalized Medicine pays non établi dans la noticeInstitution
Clinical Big Data Research Center — Sun Yat-sen University, The Seventh Affiliated Hospital of Sun Yat-sen University et State Key Laboratory of Respiratory Disease — First Affiliated Hospital of Guangzhou Medical University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.