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Peer-reviewedCC BY-NCThorax

Vitamins A and D Impact on Lung Function and Regulatory Epigenetics in Adult and Childhood Asthma

  • Rinku Sharma1
  • Priyadarshini Kachroo1,2
  • Kevin Mendez1,3
  • Qingwen Chen1
  • Julian Hecker1
  • Sofina Begum1
  • Rachel S. Kelly1
  • Ryan Smith4
  • Varun Dwaraka4
  • Juan C. Celedón5
  • Kelan Tantisira6
  • Dawn DeMeo1
3 more authors
  • Scott T. Weiss1
  • Jessica Lasky-Su1
  • Michael McGeachie1
6 affiliations
  1. 1Channing Division of network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
  2. 2Department of Health Informatics, Rutgers University School of Health Professions, Stanley S. Bergen Building, Suite 169 65 Bergen Street, Newark, NJ, USA
  3. 3Department of Chemistry, Edith Cowan University, Perth Australia
  4. 4TruDiagnostic, Inc., Lexington, KY USA
  5. 5Division of Pediatric Pulmonary Medicine, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, PA, USA
  6. 6Division of Pediatric Respiratory Medicine, University of California San Diego and Rady Children’s Hospital, San Diego, CA
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Abstract

Objective Vitamins A and D regulate numerous genes through intersecting metabolic pathways, influencing lung development and asthma. This article aimed to examine the impact of vitamins A and D on lung function, epigenetic ageing and regulatory epigenetics in children and adults with asthma. Methods Two asthma cohorts, GACRS (Genetic Epidemiology of Asthma in Costa Rica Study; 1165 children) and ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma; 1041 adults) were included. Serum miRNA profiles, blood DNA methylation and plasma/serum vitamin A and D levels were measured. Associations between vitamin levels and lung function (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC), miRNA expression and DNA methylation were evaluated. In adults, mediation analysis assessed whether methylation status and miRNAs mediated the relationship between vitamins and lung function or epigenetic ageing. Results In children, higher vitamin A was associated with higher FEV 1 (β=2.5, p=4.9 × 10 -3 ) and FVC (β=7.6, p=7.7 × 10 -14 ) but lower FEV 1 /FVC (β=−3.9, p=2.0 × 10 -16 ); vitamin D showed no association. In adults, both vitamins were positively associated with FEV 1 (vitamin A: β=4.7, p=9.3 × 10 -3 , vitamin D: β=0.16, p=8.6 × 10 -3 ) and FVC (vitamin A: β=3.4, p=3.0 × 10 -2 , vitamin D: β=0.18, p=4.6 × 10 -4 ); only vitamin A was associated with FEV 1 /FVC (vitamin A: β=2.5, p=3.9 × 10 -2 ). Vitamin D sufficiency corresponded to lower epigenetic ageing in adults. Higher vitamin levels were associated with IRF5 regulatory cytosine hypomethylation at cytosine-guanine dinucleotides (CpG), corresponding to better lung function and lower ageing. Distinct vitamin-associated miRNAs were identified, with shared targets enriched in immune and cell-cycle pathways. Mediation analyses indicated statistical partial effects through methylation and miRNAs. Conclusions Vitamin A, but not vitamin D, in children was associated with better lung function and lower epigenetic ageing in asthma, with effects mediated by DNA methylation and miRNA regulation.

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Cite

BibTeXRIS
BibTeX
@article{sharma2026vitamins,
  title = {{Vitamins A and D Impact on Lung Function and Regulatory Epigenetics in Adult and Childhood Asthma}},
  author = {Rinku Sharma and Priyadarshini Kachroo and Kevin Mendez and Qingwen Chen and Julian Hecker and Sofina Begum and Rachel S. Kelly and Ryan Smith and Varun Dwaraka and Juan C. Celedón and Kelan Tantisira and Dawn DeMeo and Scott T. Weiss and Jessica Lasky-Su and Michael McGeachie},
  journal = {Thorax},
  year = {2026},
  month = jun,
  doi = {10.1136/thorax-2025-223756},
  url = {https://doi.org/10.1136/thorax-2025-223756},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Vitamins A and D Impact on Lung Function and Regulatory Epigenetics in Adult and Childhood Asthma
AU  - Rinku Sharma
AU  - Priyadarshini Kachroo
AU  - Kevin Mendez
AU  - Qingwen Chen
AU  - Julian Hecker
AU  - Sofina Begum
AU  - Rachel S. Kelly
AU  - Ryan Smith
AU  - Varun Dwaraka
AU  - Juan C. Celedón
AU  - Kelan Tantisira
AU  - Dawn DeMeo
AU  - Scott T. Weiss
AU  - Jessica Lasky-Su
AU  - Michael McGeachie
PY  - 2026
DA  - 2026/06/30
JO  - Thorax
DO  - 10.1136/thorax-2025-223756
UR  - https://doi.org/10.1136/thorax-2025-223756
AB  - Objective Vitamins A and D regulate numerous genes through intersecting metabolic pathways, influencing lung development and asthma. This article aimed to examine the impact of vitamins A and D on lung function, epigenetic ageing and regulatory epigenetics in children and adults with asthma. Methods Two asthma cohorts, GACRS (Genetic Epidemiology of Asthma in Costa Rica Study; 1165 children) and ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma; 1041 adults) were included. Serum miRNA profiles, blood DNA methylation and plasma/serum vitamin A and D levels were measured. Associations between vitamin levels and lung function (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC), miRNA expression and DNA methylation were evaluated. In adults, mediation analysis assessed whether methylation status and miRNAs mediated the relationship between vitamins and lung function or epigenetic ageing. Results In children, higher vitamin A was associated with higher FEV 1 (β=2.5, p=4.9 × 10 -3 ) and FVC (β=7.6, p=7.7 × 10 -14 ) but lower FEV 1 /FVC (β=−3.9, p=2.0 × 10 -16 ); vitamin D showed no association. In adults, both vitamins were positively associated with FEV 1 (vitamin A: β=4.7, p=9.3 × 10 -3 , vitamin D: β=0.16, p=8.6 × 10 -3 ) and FVC (vitamin A: β=3.4, p=3.0 × 10 -2 , vitamin D: β=0.18, p=4.6 × 10 -4 ); only vitamin A was associated with FEV 1 /FVC (vitamin A: β=2.5, p=3.9 × 10 -2 ). Vitamin D sufficiency corresponded to lower epigenetic ageing in adults. Higher vitamin levels were associated with IRF5 regulatory cytosine hypomethylation at cytosine-guanine dinucleotides (CpG), corresponding to better lung function and lower ageing. Distinct vitamin-associated miRNAs were identified, with shared targets enriched in immune and cell-cycle pathways. Mediation analyses indicated statistical partial effects through methylation and miRNAs. Conclusions Vitamin A, but not vitamin D, in children was associated with better lung function and lower epigenetic ageing in asthma, with effects mediated by DNA methylation and miRNA regulation.
SN  - 0040-6376
SN  - 1468-3296
ER  -