In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 11 ( 2020-11-25), p. e0242364-
Abstract:
Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma. Methods Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing. Results Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P 〈 0.001; SAGE II: 235.99 vs. 223.07, P 〈 0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0242364
DOI:
10.1371/journal.pone.0242364.g001
DOI:
10.1371/journal.pone.0242364.g002
DOI:
10.1371/journal.pone.0242364.t001
DOI:
10.1371/journal.pone.0242364.t002
DOI:
10.1371/journal.pone.0242364.t003
DOI:
10.1371/journal.pone.0242364.t004
DOI:
10.1371/journal.pone.0242364.t005
DOI:
10.1371/journal.pone.0242364.s001
DOI:
10.1371/journal.pone.0242364.s002
DOI:
10.1371/journal.pone.0242364.s003
DOI:
10.1371/journal.pone.0242364.s004
DOI:
10.1371/journal.pone.0242364.s005
DOI:
10.1371/journal.pone.0242364.s006
DOI:
10.1371/journal.pone.0242364.s007
DOI:
10.1371/journal.pone.0242364.s008
DOI:
10.1371/journal.pone.0242364.s009
DOI:
10.1371/journal.pone.0242364.s010
DOI:
10.1371/journal.pone.0242364.s011
DOI:
10.1371/journal.pone.0242364.s012
DOI:
10.1371/journal.pone.0242364.s013
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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