Circulating miRNAs associate with historical childhood asthma hospitalization in different serum vitamin D groups
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Published:2024-03-08
Issue:1
Volume:25
Page:
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ISSN:1465-993X
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Container-title:Respiratory Research
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language:en
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Short-container-title:Respir Res
Author:
Hong Xiaoning,Jiang Mingye,Kho Alvin T.,Tiwari Anshul,Guo Haiyan,Wang Alberta L.,McGeachie Michael J.,Weiss Scott T.,Tantisira Kelan G.,Li Jiang
Abstract
Abstract
Background
Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels.
Methods
We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA).
Results
We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels.
Conclusions
miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.
Funder
NIH
Seventh Affiliated Hospital of Sun Yan-Sen University
Shenzhen Key Laboratory of Chinese Medicine Active substance screening and Translational Research
Shenzhen Science and Technology Innovation Program
Publisher
Springer Science and Business Media LLC