Mitochondrial DNA variants and pulmonary function in older persons

Carlos A. Vaz Fragoso*, Todd M. Manini, John A. Kairalla, Thomas W. Buford, Fang Chi Hsu, Thomas M. Gill, Stephen B. Kritchevsky, Mary M. McDermott, Jason L. Sanders, Steven R. Cummings, Gregory J. Tranah

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: We provide the first examination of mitochondrial DNA (mtDNA) variants and pulmonary function in older persons. Methods: Cross-sectional associations between mtDNA variants and pulmonary function were evaluated as a combined p-values meta-analysis, using data from two independent cohorts of older persons. The latter included white and black participants, aged ≥70 years, from the Lifestyle Interventions and Independence for Elders study (LIFE) (N = 1247) and the Health, Aging and Body Composition study (Health ABC) (N = 731), respectively. Pulmonary function included the forced expiratory volume in one-second as a Z-score (FEV1z) and the maximal inspiratory pressure (MIP) in cm of water. Results: In black participants, significant associations were found between mtDNA variants and MIP: m.7146A > G, COI (p = 3E-5); m.7389 T > C, COI (p = 2E-4); m.15301G > A, CYB (p = 9E-5); m.16265A > G, HV1 (p = 9E-5); meta-analytical p-values <0.0002. Importantly, these mtDNA variants were unique to black participants and were not present in white participants. Moreover, in black participants, aggregate genetic effects on MIP were observed across mutations in oxidative phosphorylation complex IV (p = 0.004), complex V (p = 0.0007), and hypervariable (p = 0.003) regions. The individual and aggregate variant results were significant after adjustment for multiple comparisons. Otherwise, no significant associations were detected for MIP in whites or for FEV1z in whites or blacks. Conclusions: We have shown that mtDNA variants of African origin are cross-sectionally associated with MIP, a measure of respiratory muscle strength. Thus, our results establish the rationale for longitudinal studies to evaluate whether mtDNA variants of African origin identify those at risk of subsequently developing a respiratory muscle impairment (lower MIP values).

Original languageEnglish (US)
Pages (from-to)96-103
Number of pages8
JournalExperimental Gerontology
Volume115
DOIs
Publication statusPublished - Jan 2019

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Keywords

  • Aging
  • Mitochondrial DNA
  • Pulmonary function

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Vaz Fragoso, C. A., Manini, T. M., Kairalla, J. A., Buford, T. W., Hsu, F. C., Gill, T. M., ... Tranah, G. J. (2019). Mitochondrial DNA variants and pulmonary function in older persons. Experimental Gerontology, 115, 96-103. https://doi.org/10.1016/j.exger.2018.11.023