| 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 |
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 investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations.</p>
METHODS: mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703).</p>
RESULTS: Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, -0.006 [95% confidence interval, -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 individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], P = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN.</p>
CONCLUSION: mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.</p>
12 Keywords
- Adult
- Aged
- Asthma
- Cohort Studies
- DNA Copy Number Variations
- DNA, Mitochondrial
- Disease Progression
- Female
- Humans
- Male
- Middle Aged
- Severity of Illness Index
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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