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Genetic variants predicting aerobic capacity response to training are also associated with skeletal muscle oxidative capacity in moderate-to-severe COPD.

ABSTRACT: Muscle oxidative capacity is a major determinant of maximum oxygen uptake (V?O2max). V?O2max predicts survival in humans. Muscle oxidative capacity is low in chronic obstructive pulmonary disease (COPD) and can be assessed from the muscle oxygen consumption recovery rate constant ( k) by near-infrared spectroscopy. We hypothesized that 11 SNPs, previously associated with the increase in V?O2max following exercise training, would correlate with k in 152 non-Hispanic White and African American smokers with and without COPD. Associations were adjusted for age, weight, FEV1% predicted, steps/day, and principal components of genetic ancestry. No SNPs were significantly associated with k. rs2792022 within BTAF1 (??=?0.130, P = 0.053) and rs24575771 within SLC22A3 (??=?0.106, P = 0.058) approached nominal significance. Case-control stratification identified three SNPs nominally associated with k in moderate-to-severe COPD ( rs6481619 within SVIL ??=?0.152, P = 0.013; BTAF1 ??=?0.196, P = 0.046; rs7386139 within DEPTOR ??=?0.159, P = 0.047). These data support further study of the genomic contributions to skeletal muscle dysfunction in COPD.

SUBMITTER: Adami A

PROVIDER: S-EPMC6172613 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Genetic variants predicting aerobic capacity response to training are also associated with skeletal muscle oxidative capacity in moderate-to-severe COPD.

Adami Alessandra A Hobbs Brian D BD McDonald Merry-Lynn N MN Casaburi Richard R Rossiter Harry B HB

Physiological genomics 20180525 9

Muscle oxidative capacity is a major determinant of maximum oxygen uptake (V̇O2max). V̇O2max predicts survival in humans. Muscle oxidative capacity is low in chronic obstructive pulmonary disease (COPD) and can be assessed from the muscle oxygen consumption recovery rate constant ( k) by near-infrared spectroscopy. We hypothesized that 11 SNPs, previously associated with the increase in V̇O2max following exercise training, would correlate with k in 152 non-Hispan ...[more]

PMID: 29799805

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Project description:PurposeChronic obstructive pulmonary disease (COPD) is associated with altered metabolism and body composition that accompany poor outcomes. We aimed to determine whether metabolic derangements in COPD are associated with skeletal muscle deconditioning and/or physical inactivity, independent of pulmonary obstruction.MethodsWe characterized serum metabolites associated with muscle oxidative capacity or physical activity in 44 COPD patients (forced expiratory volume in 1 s [FEV1] = 61% ± 4% predicted) and 63 current and former smokers with normal spirometry (CON) (FEV1 = 93% ± 2% predicted). Medial gastrocnemius oxidative capacity was assessed at rest from the recovery rate constant (k) of muscle oxygen consumption using near-infrared spectroscopy. Step counts and physical activity (average vector magnitude units [VMU] per minute) were measured over 5-7 d using triaxial accelerometry. Untargeted prime and lipid metabolites were measured using liquid chromatography and mass spectrometry.ResultsMuscle k (1.12 ± 0.05 vs 1.68 ± 0.06 min, P < 0.0001, d = 1.58) and VMU per minute (170 ± 26 vs 450 ± 50 VMU per minute, P = 0.004, d = 1.04) were lower in severe COPD (FEV1 < 50% predicted, n = 14-16) compared with CON (n = 56-60). A total of 129 prime metabolites and 470 lipids with known identity were quantified. Using sex as a covariate, lipidomics revealed 24 differentially expressed lipids (19 sphingomyelins) in COPD, consequent to a diminished sex difference of sphingomyelins in COPD (false discovery rate [FDR] < 0.05, n = 44). Total, and some individual, fatty acid concentrations were greater in severe COPD than CON (FDR < 0.05, n = 16, d = 0.56-1.02). After adjusting for FEV1% predicted, we observed that grouped diacylglycerides (? = -0.745, FDR = 0.03) and triacylglycerides (? = -0.811, FDR = 0.01) were negatively associated with muscle oxidative capacity, but not physical activity, in severe COPD (n = 14).ConclusionStrong negative associations relate impaired mitochondrial function to the accumulation of serum aclyglycerides in severe COPD.

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Genetic variants predicting aerobic capacity response to training are also associated with skeletal muscle oxidative capacity in moderate-to-severe COPD.

Publications

Genetic variants predicting aerobic capacity response to training are also associated with skeletal muscle oxidative capacity in moderate-to-severe COPD.

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