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

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) using 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-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 (β=0.130, p=0.053) and rs 24575771 within SLC22A3 (β=0.106, p=0.058) approached nominal significance. Case-control stratification identified 3 SNPs nominally associated with k in moderate-to-severe COPD (rs6481619 within SVIL β=0.152, p=0.013; BTAF1 β=0.196, p=0.046 and rs7386139 within DEPTOR β=0.159, p=0.047). These data support further study of the genomic contributions to skeletal muscle dysfunction in COPD.