Using Molecular Classification to Predict Gains in Maximal Aerobic Capacity Following Endurance Exercise Training in Hum

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CLINICAL TRIAL REPORT

Using Molecular Classification to Predict Gains in Maximal Aerobic Capacity Following Endurance Exercise Training in Humans Vaughn W. Barry & Timothy Church & Steven N. Blair

Published online: 7 July 2010 # Springer Science+Business Media, LLC 2010

Timmons JA, Knudsen S, Rankinen T, et al.: Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 2010; doi:10.1152/japplphysiol.01295.2009.

framework that may link significant genetic components affecting exercise capacity adaptations to cardiovascular disease and other disease pathways.

Aims Rating ••Of major importance.

This study sought to find genotypic variations that contribute to differing VO2max adaptations to exercise.

Introduction

Methods

Low aerobic exercise capacity is significantly associated with elevated risk of cardiovascular disease, diabetes, cancer, and numerous other health problems. Increases in maximal oxygen uptake with aerobic training are quite variable (0% to>100%), with approximately 50% of the variance being genetically determined. Understanding the genetic contribution to exercise training adaptations presents a great opportunity for contributing to a molecular

A novel technique using RNA expression-based profiling was performed to identify molecular classifiers that predicted change. Using this approach, two independent trials identified and validated specific RNA classifiers associated with aerobic capacity changes. In the first trial, 24 young sedentary healthy white men completed a supervised 6week training program where they cycled for 45 min at 70% of their individual pre-trained VO2max on 4 days per week. Changes in maximal oxygen uptake were related to baseline RNA expression using a correlation analysis. The top RNA classifiers identified during this trial were blindly validated in the second trial, which consisted of 17 young active white individuals. These participants completed a maximal aerobic capacity test, moderate to vigorous continuous exercise, and vigorous interval training each week for 12 weeks. The adherence to training regimen was 100% in both trials. Data from the Health, Risk factors, Exercise Training and Genetics (HERITAGE) Family Study was used to genotype the validated RNA probe-sets [1]. In this trial, participants completed a 20-week exercise training program that gradually increased the volume of cycling to 50 min at

V. W. Barry (*) Exercise Science Department, University of South Carolina, 921 Assembly Street, Columbia, SC 29208, USA e-mail: [email protected] T. Church Pennington Biomedical Research Center, Baton Rouge, LA, USA e-mail: [email protected] S. N. Blair University of South Carolina, Columbia, SC, USA e-mail: [email protected]

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75% VO2max on 3 days per week. For this analysis, a subset of 473 sedentary white participants from 99 families were utilized. Exercise tests were performed before and after the training program to determine changes in aerobic power. The tot