Journal article
Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort
JCI insight, Vol.5(3), e133984
02/13/2020
DOI: 10.1172/jci.insight.133984
PMCID: PMC7098791
PMID: 31895696
Abstract
BACKGROUND. Mitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown.
METHODS. Cell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters — including FEV1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure — were examined.
RESULTS. U-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.
CONCLUSION. U-mtDNA levels may help to identify distinct clinical phenotypes and underlying pathobiological differences in males versus females with COPD.
Details
- Title: Subtitle
- Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort
- Creators
- William Z. Zhang - NewYork–Presbyterian HospitalMichelle C. Rice - Cornell UniversityKatherine L. Hoffman - Cornell UniversityClara Oromendia - Cornell UniversityIgor Z. Barjaktarevic - University of California, Los AngelesJ. Michael Wells - University of Alabama at BirminghamAnnette T. Hastie - Wake Forest UniversityWassim W. Labaki - University of Michigan Medical SchoolChristopher B. Cooper - University of California, Los AngelesAlejandro P. Comellas - University of IowaGerard J. Criner - Temple UniversityJerry A. Krishnan - University of Illinois Hospital & Health Sciences SystemRobert Paine - University of UtahNadia N. Hansel - Johns Hopkins MedicineRussell P. Bowler - University of DenverR. Graham Barr - Columbia University Irving Medical CenterStephen P. Peters - Wake Forest UniversityPrescott G. Woodruff - University of California, BerkeleyJeffrey L. Curtis - University of Michigan Medical SchoolMeilan K. Han - University of Michigan Medical SchoolKarla V. Ballman - Cornell UniversityFernando J. Martinez - Cornell UniversityAugustine M.K. Choi - Houston MethodistKiichi Nakahira - Cornell UniversitySuzanne M. Cloonan - Cornell UniversityMary E. Choi - NewYork–Presbyterian HospitalSPIROMICS Investigators
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.5(3), e133984
- DOI
- 10.1172/jci.insight.133984
- PMID
- 31895696
- PMCID
- PMC7098791
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- American Society for Clinical Investigation
- Grant note
- HHSN268200900013C,HHSN268200900014C,HHSN268200900015C,HHSN268200900016C,HHSN268200900017C,HHSN268200900018C,HHSN268200900019C,HHSN268200900020C / NIH/NHLBI U01 HL137880,U24 HL141762 / NIH/NHLBI
- Language
- English
- Date published
- 02/13/2020
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984359567502771
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