Genetic variants predicting the response to endurance exercise training are also associated with skeletal muscle oxidative capacity in COPD
| Autor: | Harry B. Rossiter, Merry-Lynn McDonald, William W. Stringer, Alessandra Adami, Edwin K. Silverman, Janos Porszasz, Brian D. Hobbs, Michael H. Cho, Richard Casaburi |
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| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
COPD business.industry CPVL Skeletal muscle Single-nucleotide polymorphism medicine.disease 03 medical and health sciences 0302 clinical medicine Endocrinology medicine.anatomical_structure 030228 respiratory system Endurance training Internal medicine Myocyte Medicine 030212 general & internal medicine Risk factor business Aerobic capacity |
| Zdroj: | Clinical Respiratory Physiology, Exercise and Functional Imaging. |
| Popis: | Introduction: Low aerobic capacity is a strong mortality risk factor. A large fraction of variance in aerobic capacity gained by exercise training is accounted for by 11 single nucleotide polymorphisms (SNPs; Timmons et al. PMC2886694). COPD is associated with loss of skeletal muscle oxidative capacity. We hypothesized that 11 SNPs previously associated with training responsiveness would be associated with low muscle oxidative capacity in COPD. Methods: Calf oxidative capacity was assessed at rest from the O 2 consumption recovery rate constant ( k ) by near-infrared spectroscopy in 195 COPDGene participants; 90 with COPD (GOLD 1-4, n=28/34/18/10). Greater k reflects greater oxidative capacity. Genetic association analyses were adjusted for age, weight, FEV 1 %pred and physical activity (triaxial accelerometry). Results: k was lower in COPD (1.27±0.39 min −1 ) than controls (1.68±0.49 min −1 , p k in Non-Hispanic Whites: rs7386139 within DEPDC6 (b=.19, p=.03) and rs2792022 within BTAF1 (b=-.18, p=.02). Two SNPs were nominally associated with k in African Americans: rs10497520 in TTN (b=-.22, p=.04) and rs4257918 in CPVL (b=-.36, p=.005). Conclusions: Genetic variants associated with training-induced gain in aerobic capacity may be associated with low muscle oxidative capacity in COPD. Of relevance, DEPDC6 is associated with myofiber switch from oxidative to glycolytic metabolism, and TTN (titin) is associated muscle passive stiffness and elasticity. Larger populations and mechanistic studies are needed to further assess these findings. Support: NIH HL089856, HL089897; SNF-P300P_151705; ATS-2014-03; PBF Foundation |
| Databáze: | OpenAIRE |
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