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Mitochondrial DNA Copy Number Variation in Asthma Risk, Severity, and Exacerbations. | LitMetric

AI Article Synopsis

  • - The study explores the connection between mitochondrial dysfunction, indicated by mitochondrial DNA copy number (mtDNA-CN), and asthma diagnosis, severity, and exacerbations.
  • - Results show that asthmatics have lower mtDNA-CN compared to non-asthmatics, but severity levels in asthma do not influence mtDNA-CN.
  • - Higher mtDNA-CN is linked to a reduced risk of severe asthma exacerbations, emphasizing the potential importance of mitochondrial function in asthma management.

Article Abstract

Rationale: Although airway oxidative stress and inflammation are central to asthma pathogenesis, there is limited knowledge of the relationship of asthma risk, severity, or exacerbations to mitochondrial dysfunction, which is pivotal to oxidant generation and inflammation.

Objectives: We investigated whether mitochondrial DNA copy number (mtDNA-CN) as a measure of mitochondrial function is associated with asthma diagnosis, severity, oxidative stress, and exacerbations.

Methods: We measured mtDNA-CN in blood in two cohorts. In the UK Biobank (UKB), we compared mtDNA-CN in mild and moderate-severe asthmatics to non-asthmatics. In the Severe Asthma Research Program (SARP), we evaluated mtDNA-CN in relation to asthma severity, biomarkers of oxidative stress and inflammation, and exacerbations.

Measures And Main Results: In UK Biobank, asthmatics ( = 29,768) have lower mtDNA-CN compared to non-asthmatics ( = 239,158) (beta, -0.026 [95% CI, -0.038 to -0.014], = 2.46×10). While lower mtDNA-CN is associated with asthma, mtDNA-CN did not differ by asthma severity in either UKB or SARP. Biomarkers of inflammation show that asthmatics have higher white blood cells (WBC), neutrophils, eosinophils, fraction exhaled nitric oxide (FNO), and lower superoxide dismutase (SOD) than non-asthmatics, confirming greater oxidative stress in asthma. In one year follow-up in SARP, higher mtDNA-CN is associated with reduced risk of three or more exacerbations in the subsequent year (OR 0.352 [95% CI, 0.164 to 0.753], = 0.007).

Conclusions: Asthma is characterized by mitochondrial dysfunction. Higher mtDNA-CN identifies an exacerbation-resistant asthma phenotype, suggesting mitochondrial function is important in exacerbation risk.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10723502PMC
http://dx.doi.org/10.1101/2023.12.05.23299392DOI Listing

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