Objective. To determine whether genetic variants suggested by the literature to be associated with physiology and fitness phenotypes predicted differential physiological and subjective responses to a bout of aerobic exercise among inactive but otherwise healthy adults. Method. Participants completed a 30-minute submaximal aerobic exercise session. Measures of physiological and subjective responding were taken before, during, and after exercise. 14 single nucleotide polymorphisms (SNPs) that have been previously associated with various exercise phenotypes were tested for associations with physiological and subjective response to exercise phenotypes. Results. We found that two SNPs in the FTO gene (rs8044769 and rs3751812) were related to positive affect change during exercise. Two SNPs in the CREB1 gene (rs2253206 and 2360969) were related to change in temperature during exercise and with maximal oxygen capacity (VO2 max). The SLIT2 SNP rs1379659 and the FAM5C SNP rs1935881 were associated with norepinephrine change during exercise. Finally, the OPRM1 SNP rs1799971 was related to changes in norepinephrine, lactate, and rate of perceived exertion (RPE) during exercise. Conclusion. Genetic factors influence both physiological and subjective responses to exercise. A better understanding of genetic factors underlying physiological and subjective responses to aerobic exercise has implications for development and potential tailoring of exercise interventions. 1. Introduction In the United States, insufficient participation in leisure time physical activity constitutes a major threat to public health. Recent estimates suggest that 25% of Americans do not engage in any physical activity at all [1]. Even those engaging in physical activity are usually not doing so at recommended levels. In order to promote and maintain health, the American College of Sports Medicine (ACSM) recommends a minimum of 30 minutes of moderate intensity aerobic physical activity five days a week or a minimum of 20 minutes of vigorous intensity aerobic physical activity three days a week [2]. Despite these widely disseminated guidelines, the Centers for Disease Control (CDC) report that Americans have made “no substantial progress towards achieving recommended levels of physical activity” with the proportion of 18–29 year olds meeting guidelines hovering around 35% and the proportion of adults 65 and older meeting guidelines at about 20% [1]. These numbers are troubling, as aerobic exercise has been convincingly linked to the prevention of myriad negative health outcomes, including
References
[1]
Health, United States, 2008: With Chartbook, The National Center for Health Statistics, Hyattsville, Md, USA, 2009.
[2]
W. L. Haskell, I. M. Lee, R. R. Pate et al., “Physical activity and public health: updated recommendation for adults from the American college of sports medicine and the American heart association,” Circulation, vol. 116, no. 9, pp. 1081–1093, 2007.
[3]
C. M. Friedenreich, H. K. Neilson, and B. M. Lynch, “State of the epidemiological evidence on physical activity and cancer prevention,” European Journal of Cancer, vol. 46, no. 14, pp. 2593–2604, 2010.
[4]
C. M. Friedenreich, C. G. Woolcott, A. McTiernan et al., “Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women,” Journal of Clinical Oncology, vol. 28, no. 9, pp. 1458–1466, 2010.
[5]
B. M. Lynch, H. K. Neilson, and C. M. Friedenreich, “Physical activity and breast cancer prevention,” Recent Results in Cancer Research, vol. 186, pp. 13–42, 2011.
[6]
K. Y. Wolin, A. V. Patel, P. T. Campbell et al., “Change in physical activity and colon cancer incidence and mortality,” Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 12, pp. 3000–3004, 2010.
[7]
C. M. Friedenreich and M. R. Orenstein, “Physical activity and cancer prevention: etiologic evidence and biological mechanisms,” Journal of Nutrition, vol. 132, supplement 11, pp. 3456S–3464S, 2002.
[8]
I. M. Lee, “Physical activity and cancer prevention—data from epidemiologic studies,” Medicine and Science in Sports and Exercise, vol. 35, no. 11, pp. 1823–1827, 2003.
[9]
D. M. Parkin, “Cancers attributable to inadequate physical exercise in the UK in 2010,” British Journal of Cancer, vol. 105, supplement 2, pp. S38–S41, 2011.
[10]
M. Esteller, “Cancer epigenomics: DNA methylomes and histone-modification maps,” Nature Reviews Genetics, vol. 8, no. 4, pp. 286–298, 2007.
[11]
M. Rodríguez-Paredes and M. Esteller, “Cancer epigenetics reaches mainstream oncology,” Nature Medicine, vol. 17, no. 3, pp. 330–339, 2011.
[12]
National Cancer Institute, Fact Sheet: Physical Activity and Cancer, http://www.cancer.gov/cancertopics/factsheet/prevention/physicalactivity, 2009.
[13]
S. Michie, C. Abraham, C. Whittington, J. McAteer, and S. Gupta, “Effective techniques in healthy eating and physical activity interventions: a meta-regression,” Health Psychology, vol. 28, no. 6, pp. 690–701, 2009.
[14]
P. Ekkekakis, G. Parfitt, and S. J. Petruzzello, “The pleasure and displeasure people feel when they exercise at different intensities: decennial update and progress towards a tripartite rationale for exercise intensity prescription,” Sports Medicine, vol. 41, no. 8, pp. 641–671, 2011.
[15]
J. Buckworth and R. . Dishman, “Exercise adherence,” in Handbook of Sport Psychology, R. C. Eklund, Ed., pp. 509–536, Wiley, Hoboken, NJ, USA, 2007.
[16]
A. Bryan, K. E. Hutchison, D. R. Seals, and D. L. Allen, “A transdisciplinary model integrating genetic, physiological, and psychological correlates of voluntary exercise,” Health Psychology, vol. 26, no. 1, pp. 30–39, 2007.
[17]
A. D. Bryan, A. E. C. Hooper, J. Ciccolo, B. Marcus, K. E. Hutchison, and R. E. Magnan, “Colorado Stride (COStride): genetic and physiological moderators of response to an intervention to increase physical activity,” In press.
[18]
F. Booth and P. D. Neufer, “Exercise genomics and proteomics,” in ACSM's Advanced Exercise Physiology, C. M. Tipton, Ed., Lipincott, Williams & Wilkins, Baltimore, Md, USA, 2006.
[19]
B. M. Kwan and A. D. Bryan, “Affective response to exercise as a component of exercise motivation: attitudes, norms, self-efficacy, and temporal stability of intentions,” Psychology of Sport and Exercise, vol. 11, no. 1, pp. 71–79, 2010.
[20]
D. M. Williams, S. Dunsiger, J. T. Ciccolo, B. A. Lewis, A. E. Albrecht, and B. H. Marcus, “Acute affective response to a moderate-intensity exercise stimulus predicts physical activity participation 6 and 12 months later,” Psychology of Sport and Exercise, vol. 9, no. 3, pp. 231–245, 2008.
[21]
E. J. C. de Geus and M. H. M. de Moor, “A genetic perspective on the association between exercise and mental health,” Mental Health and Physical Activity, vol. 1, no. 2, pp. 53–61, 2008.
[22]
J. H. Stubbe, D. I. Boomsma, J. M. Vink et al., “Genetic influences on exercise participation in 37.051 twin pairs from seven countries,” PLoS ONE, vol. 1, no. 1, Article ID e22, 2006.
[23]
T. D. Cannon and M. C. Keller, “Endophenotypes in the genetic analyses of mental disorders,” Annual Review of Clinical Psychology, vol. 2, pp. 267–290, 2006.
[24]
J. W. Bea, T. G. Lohman, E. C. Cussler, S. B. Going, and P. A. Thompson, “Lifestyle modifies the relationship between body composition and adrenergic receptor genetic polymorphisms, ADRB2, ADRB3 and ADRA2B: a secondary analysis of a randomized controlled trial of physical activity among postmenopausal women,” Behavior Genetics, vol. 40, no. 5, pp. 649–659, 2010.
[25]
T. O. Kilpelainen, D. E. Laaksonen, T. A. Lakka et al., “The rs1800629 polymorphism in the TNF gene interacts with physical activity on the changes in C-reactive protein levels in the finnish diabetes prevention study,” Experimental and Clinical Endocrinology and Diabetes, vol. 118, no. 10, pp. 757–759, 2010.
[26]
D. A. Phares, A. A. Halverstadt, A. R. Shuldiner et al., “Association between body fat response to exercise training and multilocus ADR genotypes,” Obesity Research, vol. 12, no. 5, pp. 807–815, 2004.
[27]
P. An, T. Rice, J. Gagnon et al., “Familial aggregation of stroke volume and cardiac output during submaximal exercise: the HERITAGE family study,” International Journal of Sports Medicine, vol. 21, no. 8, pp. 566–572, 2000.
[28]
C. Bouchard, E. Warwick Daw, T. Rice et al., “Familial resemblance for VO2(2max) in the sedentary state: the HERITAHE family study,” Medicine and Science in Sports and Exercise, vol. 30, no. 2, pp. 252–258, 1998.
[29]
S. E. Gaskill, T. Rice, C. Bouchard et al., “Familial resemblance in ventilatory threshold: the HERITAGE Family Study,” Medicine and Science in Sports and Exercise, vol. 33, no. 11, pp. 1832–1840, 2001.
[30]
L. Perusse, J. Gagnon, M. A. Province et al., “Familial aggregation of submaximal aerobic performance in the heritage family study,” Medicine and Science in Sports and Exercise, vol. 33, no. 4, pp. 597–604, 2001.
[31]
D. G. MacArthur and K. N. North, “Genes and human elite athletic performance,” Human Genetics, vol. 116, no. 5, pp. 331–339, 2005.
[32]
A. K. Travlos and D. Q. Marisi, “Perceived exertion during physical exercise among individuals high and low in fitness,” Perceptual and Motor Skills, vol. 84, no. 2, pp. 419–424, 1996.
[33]
A. Scuteri, S. Sanna, W. M. Chen et al., “Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.,” PLoS genetics, vol. 3, no. 7, Article ID e115, 2007.
[34]
T. Rankinen, T. Rice, M. Teran-Garcia, D. C. Rao, and C. Bouchard, “FTO genotype is associated with exercise training-induced changes in body composition,” Obesity, vol. 18, no. 2, pp. 322–326, 2010.
[35]
J. R. Speakman, K. A. Rance, and A. M. Johnstone, “Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure,” Obesity, vol. 16, no. 8, pp. 1961–1965, 2008.
[36]
R. B. Fillingim, L. Kaplan, R. Staud et al., “The A118G single nucleotide polymorphism of the μ-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans,” Journal of Pain, vol. 6, no. 3, pp. 159–167, 2005.
[37]
R. S. Vasan, M. G. Larson, J. Aragam et al., “Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study,” BMC Medical Genetics, vol. 8, supplement 1, p. S2, 2007.
[38]
T. Rankinen, G. Argyropoulos, T. Rice, D. C. Rao, and C. Bouchard, “CREB1 is a strong genetic predictor of the variation in exercise heart rate response to regular exercise: the HERITAGE Family Study,” Circulation, vol. 3, no. 3, pp. 294–299, 2010.
[39]
T. Rankinen, Y. J. Sung, M. A. Sarzynski, T. K. Rice, D. C. Rao, and C. Bouchard, “Heritability of submaximal exercise heart rate response to exercise training is accounted for by nine SNPs,” Journal of Applied Physiology, vol. 112, no. 5, pp. 892–897, 2012.
[40]
R. E. Magnan, J. T. Ciccolo, A. D. Bryan, B. H. Marcus, and R. Nilsson, “A transdisciplinary approach to the moderators of exercise behavior change,” Journal of Behavioral Medicine. In press.
[41]
D. D. Christou, C. L. Gentile, C. A. DeSouza, D. R. Seals, and P. E. Gates, “Fatness is a better predictor of cardiovascular disease risk factor profile than aerobic fitness in healthy men,” Circulation, vol. 111, no. 15, pp. 1904–1914, 2005.
[42]
American College of Sports, ACSM's Guidelines for Exercise Testing and Prescription, Lippincott Williams & Wilkins, New York, NY, USA, 2010.
[43]
C. L. Lox, S. Jackson, S. W. Tuholski, D. Wasley, and D. C. Treasure, “Revisiting the measurement of exercise-induced feeling states: the physical activity affect scale (PAAS),” Measurement in Physical Education and Exercise Science, vol. 4, no. 2, pp. 79–95, 2000.
[44]
W. J. Hardy and C. J. Rejeski, “Not what, but how one feels: the measurement of affect during exercise,” Journal of Sport & Exercise Psychology, vol. 11, no. 3, pp. 304–317, 1989.
[45]
G. Borg, Borg's Perceived Exertion and Pain Scales, Human Kinetics, Champaign, Ill, USA, 1998.
[46]
D. A. Burton, K. Stokes, and G. M. Hall, “Physiological effects of exercise. Continuing education in anaesthesia,” Critical Care & Pain, vol. 4, no. 6, pp. 185–188, 2004.
[47]
G. F. Dunton and E. Vaughan, “Anticipated Affective Consequences of Physical Activity Adoption and Maintenance,” Health Psychology, vol. 27, no. 6, pp. 703–710, 2008.
[48]
A. J. Marian, “Molecular genetic studies of complex phenotypes,” Translational Research, vol. 159, no. 2, pp. 64–79, 2012.
[49]
M. T. Hassanein, H. N. Lyon, T. T. Nguyen et al., “Fine mapping of the association with obesity at the FTO locus in African-derived populations,” Human Molecular Genetics, vol. 19, no. 14, Article ID ddq178, pp. 2907–2916, 2010.
[50]
M. R. Wing, J. Ziegler, C. D. Langefeld et al., “Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study,” Human Genetics, vol. 125, no. 5-6, pp. 615–626, 2009.
[51]
G. Thorleifsson, G. B. Walters, D. F. Gudbjartsson et al., “Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity,” Nature Genetics, vol. 41, no. 1, pp. 18–24, 2009.
[52]
J. Zhao, J. P. Bradfield, M. Li et al., “The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI,” Obesity, vol. 17, no. 12, pp. 2254–2257, 2009.
[53]
K. W. Patberg, A. Shvilkin, A. N. Plotnikov, P. Chandra, M. E. Josephson, and M. R. Rosen, “Cardiac memory: mechanisms and clinical implications,” Heart Rhythm, vol. 2, no. 12, pp. 1376–1382, 2005.
[54]
M. R. Rosen and I. S. Cohen, “Cardiac memory ... new insights into molecular mechanisms,” Journal of Physiology, vol. 570, no. 2, pp. 209–218, 2006.
[55]
H. Wu, Y. Zhou, and Z. Q. Xiong, “Transducer of regulated CREB and late phase long-term synaptic potentiation,” FEBS Journal, vol. 274, no. 13, pp. 3218–3223, 2007.
[56]
C. Bond, K. S. Laforge, M. Tian et al., “Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: possible implications for opiate addiction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 16, pp. 9608–9613, 1998.
[57]
R. F. Baumeister, K. D. Vohs, C. N. DeWall, and L. Zhang, “How emotion shapes behavior: feedback, anticipation, and reflection, rather than direct causation,” Personality and Social Psychology Review, vol. 11, no. 2, pp. 167–203, 2007.
[58]
R. Kaaks and A. Lukanova, “Effects of weight control and physical activity in cancer prevention: role of endogenous hormone metabolism,” Annals of the New York Academy of Sciences, vol. 963, pp. 268–281, 2002.
[59]
A. C. Society, Cancer Facts & Figures 2011, American Cancer Society, Atlanta, Ga, USA, 2011.
[60]
L. M. S. J. Levi, R. St. Laurent, and D. Kohn, F as in Fat: How Obesity Threatens America's Future, Robert Wood Johnson Foundation and The Trust for America's Health, Princeton, NJ, USA, 2011.
[61]
E. M. Monninkhof, S. G. Elias, F. A. Vlems et al., “Physical activity and breast cancer: a systematic review,” Epidemiology, vol. 18, no. 1, pp. 137–157, 2007.
[62]
R. A. Carels, B. Berger, and L. Darby, “The association between mood states and physical activity in postmenopausal, obese, sedentary women,” Journal of Aging and Physical Activity, vol. 14, no. 1, pp. 12–28, 2006.
[63]
P. Ekkekakis and E. Lind, “Exercise does not feel the same when you are overweight: the impact of self-selected and imposed intensity on affect and exertion,” International Journal of Obesity, vol. 30, no. 4, pp. 652–660, 2006.
[64]
P. Ekkekakis, E. Lind, and S. Vazou, “Affective responses to increasing levels of exercise intensity in normal-weight, overweight, and obese middle-aged women,” Obesity, vol. 18, no. 1, pp. 79–85, 2010.
[65]
B. M. Kwan and A. Bryan, “In-task and post-task affective response to exercise: translating exercise intentions into behaviour,” British Journal of Health Psychology, vol. 15, no. 1, pp. 115–131, 2010.
[66]
C. S. Carver and M. F. Scheier, “Control theory: a useful conceptual framework for personality-social, clinical, and health psychology,” Psychological Bulletin, vol. 92, no. 1, pp. 111–135, 1982.
