| Title: | Mitochondrial DNA Copy Number Variation in Asthma Risk, Severity, and Exacerbations |
| Journal: | Journal of Allergy and Clinical Immunology |
| Published: | 3 Sep 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39237012/ |
| DOI: | https://doi.org/10.1016/j.jaci.2024.08.022 |
| URL: | https://doi.org/10.1101/2023.12.05.23299392 |
Publication 13029
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Abstract
BACKGROUND: Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers.</p>
OBJECTIVES: We investigate whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations.</p>
METHODS: MtDNA-CN is evaluated in blood from two cohorts: UK Biobank (UKB) (asthmatics n = 39,147; non-asthmatics n = 302,302) and Severe Asthma Research Program (SARP) (n = 1283 asthmatics, non-severe n = 703).</p>
RESULTS: Asthmatics have lower mtDNA-CN compared to non-asthmatics in UKB (beta, -0.006 [95% CI, -0.008 to -0.003], P = 6.23×10-6). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in asthma than in non-asthmatics at all ages. In one-year longitudinal study in SARP, mtDNA-CN is associated with risk of exacerbation; those with highest mtDNA-CN have the lowest risk of exacerbation [OR 0.333 [95% CI, 0.173 to 0.542], P = 0.001]. Biomarkers of inflammation and oxidative stress are higher in asthma than non-asthmatics, but the lower mtDNA-CN in asthma are independent of general inflammation or oxidative stress. Mendelian Randomization (MR) studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN.</p>
CONCLUSION: MtDNA-CN are lower in asthmatics than in non-asthmatics and are associated with exacerbations. Low mtDNA-CN in asthma are not mediated through inflammation but are associated with the genetic predisposition to asthma.</p>
24 Authors
- Weiling Xu
- Yun Soo Hong
- Bo Hu
- Suzy A.A. Comhair
- Allison J. Janocha
- Joe G. Zein
- Ruoying Chen
- Deborah A. Meyers
- David T. Mauger
- Victor E. Ortega
- Eugene R. Bleecker
- Mario Castro
- Loren C. Denlinger
- John V. Fahy
- Elliot Israel
- Bruce D. Levy
- Nizar N. Jarjour
- Wendy C. Moore
- Sally E. Wenzel
- Benjamin Gaston
- Chunyu Liu
- Dan E. Arking
- Serpil C. Erzurum
- Lung National Heart
1 Application
| Application ID | Title |
|---|---|
| 17731 | A phenome-wide association study of copy number variation |
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