PriMera Scientific Surgical Research and Practice (ISSN: 2836-0028)

Review Article

Volume 1 Issue 3

Genotypes and Phenotypes Associated with Muscular Recovery: Impact of Exercise and Diet

Thais Verdi*

February 28, 2023


In recent years, significant advances in molecular biology has facilitated emerging knowledge pertaining to genetics in sport science research. Specific regions of DNA are known to influence genetic polymorphism(s) and partly explain individual variations in response to exercise stimuli and diet. Following exhaustive exercise, certain genetic variations or polymorphisms have been associated with muscle damage indices and may influence muscular recovery. The purpose of this narrative review is to outline the transcription factors of co-activators of associated polymorphisms that appear to play a role in muscle recovery. We also highlight the potential interaction of gene expression and the impact of macronutrients. Several genes (ACE, ACTN3, CCL 2 (C> T), COL5A1, CKM (A> G) have been implicated in various aspects of skeletal muscle remodeling. Individuals with specific genotypes experience changes in muscle damage and recovery rates following exercise. The contribution of heritability to a specific phenotype is likely dependent and the modality, intensity, and duration of exercise. Future research is warranted to explore multigenetic characteristics to provide a deeper molecular understanding of recovery, adaptation and nutritional modulation that may allow the identification of individuals with a greater genetic predisposition, or with a greater risk of developing muscle injuries.
Keywords: Genetic; Athletes; Sports Performance; Nutrients


  1. Aaltonen S, Kujala UM and Kaprio J. “Factors behind leisure-time physical activity behavior based on Finnish twin studies: the role of genetic and environmental influences and the role of motives”. Biomed Res Int (2014): 931820.
  2. Abreu Phablo., et al. “Adaptation of Skeletal Muscle to Physical Exercise: Molecular Consideration”. Brazilian Journal of Sports Medicine 23 (2017): 60-65.
  3. Ahmetov II., et al. “SOD2 gene polymorphism and muscle damage markers in elite athletes”. Free Radic Res 48.8 (2014): 948-55.
  4. Akimoto AK., et al. “Evaluation of gene polymorphisms in exercise-induced oxidative stress and damage”. Free Radic Res 44.3 (2010): 322-31.
  5. Andersen MB., et al. “Interleukin-6: a growth factor stimulating collagen synthesis in human tendon”. J Appl Physiol 110.6 (2011): 1549-54.
  6. Andreassen CS., et al. “Accelerated atrophy of lower leg and foot muscles--a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)”. Diabetologia. 52(6) (2009): 1182-91.
  7. Aragon AA., et al. “International society of sports nutrition position stand: diets and body composition”. J Int Soc Sports Nutr 14 (2017): 16.
  8. Armstrong RB, Warren GL and Warren JA. “Mechanisms of exercise-induced muscle fibre injury”. Sports Med 12.3 (1991): 184-207.
  9. Batavani MR., et al. “Comparison of Muscle-Specific Creatine Kinase (CK-MM) Gene Polymorphism (rs8111989) Among Professional, Amateur Athletes and Non-athlete Karatekas, Asian”. J Sports Med 8.2 (2017): e43210.
  10. Baumert P., et al. “Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing”. J Appl Physiol 116 (2016): 1595-1625.
  11. Bartolomei S., et al. “Comparison of the recovery response from high-intensity and high-volume resistance exercise in trained men”. Eur J Appl Physiol 117.7 (2017): 1287-1298.
  12. Beelen M, Cermak NM and van Loon LJ. “Carbohydrate intake during and after high-intensity exercise [Performance enhancement by carbohydrate intake during sport: effects of carbohydrates during and after high-intensity exercise]”. Ned Tijdschr Geneeskd 159 (2015): A7465.
  13. Bergouignan A., et al. “Regulation of energy balance during long-term physical inactivity induced by bed rest with and without exercise training”. J Clin Endocrinol Metab 95.3 (2010): 1045-53.
  14. Bingham CO 3rd. “The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation”. J Rheumatol Suppl (2002): 3-9.
  15. Bonen A, Dyck DJ and Luiken JJ. “Skeletal muscle fatty acid transport and transporters”. Adv Exp Med Biol 441 (1998): 193-205.
  16. Brown S, Day S and Donnelly A. “Indirect evidence of human skeletal muscle damage and collagen breakdown after eccentric muscle actions”. J Sports Sci 17.5 (1999): 397-402.
  17. Clarkson PM., et al. “ACTN3 and MLCK genotype associations with exertional muscle damage”. J Appl Physio 2 (2005): 564-9.
  18. Chimienti F., et al. “Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules”. Diabetes 53.9 (2004): 2330-7.
  19. Coffey VG., et al. “Effect of consecutive repeated sprint and resistance exercise bouts on acute adaptive responses in human skeletal muscle”. Am J Physiol Regul Integr Comp Physiol 5 (2009): R1441-51.
  20. Cousins RJ. “Nutritional regulation of gene expression”. Am J Med 106.1A (1999): 20S-23S.
  21. Costill DL., et al. “Impaired muscle glycogen resynthesis after eccentric exercise”. J Appl Physiol 69.1 (1990): 46-50.
  22. Cluberton LJ., et al. “Effect of carbohydrate inges-tion on exercise-induced alterations in metabolic gene expression”. J Appl Physiol 99.4 (2005): 1359-63.
  23. Deniro M and Al-Mohanna FA. “Zinc transporter 8 (ZnT8) expression is reduced by is-chemic insults: a potential therapeutic target to prevent ischemic retinopathy”. PloS one 7.11 (2012): e50360.
  24. Dennis RA., et al. “Interleukin-1 polymorphisms are associated with the inflammatory response in human muscle to acute resistance exercise”. The Journal of physiology 560.Pt 3 (2004): 617-626.
  25. Eider J., et al. “CKM gene polymorphism in Russian and Polish rowers”. Genetika 51.3 (2015): 389-92.
  26. El-Sohemy A. “Only DNA-based dietary advice improved adherence to the Mediterranean diet score”. Am J Clin Nutr 105.3 (2017): 770.
  27. Eynon N., et al. “Genes and elite athletes: a roadmap for future research”. J Physiol 589.Pt 13 (2011): 3063-70.
  28. Fedotovskaia ON., et al. “Association of the muscle-specific creatine kinase (CKMM) gene polymorphism with physical performance of athletes]”. Fiziol Cheloveka 1 (2012): 105-9.
  29. Ferrando AA., et al. “Prolonged bed rest decreases skeletal muscle and whole body protein synthesis”. Am J Physiol 270.4 Pt 1 (1996): E627-33.
  30. Frankenfield D. “Energy expenditure and protein requirements after traumatic injury”. Nutr Clin Pract 21.5 (2006): 430-7.
  31. Fujita S., et al. “Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability”. Am J Physiol Endocrinol Metab 291.4 (2005): E745-54.
  32. Funghetto SS., et al. “Interleukin-6 -174G/C gene polymorphism affects muscle damage response to acute eccentric resistance exercise in elderly obese women”. Experimental Gerontology 48.11 (2013): 1255-1259.
  33. Garaulet M., et al. “PPARγ Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based on the Mediterranean diet”. Mol Nutr Food Res 55.12 (2001): 1771-9.
  34. Gordon PM., et al. “Resistance exercise training influences skeletal muscle immune activation: a micro-array analysis”. J Appl Physiol 112.3 (2011): 443-53.
  35. Goss AM., et al. “Effects of diet macronutrient composition on body composition and fat distribution during weight maintenance and weight loss”. Obesity (Silver Spring) 21.6 (2013): 1139-42.
  36. Grassi B., et al. Faster O? uptake kinetics in canine skeletal muscle in situ after acute creatine kinase inhibition. J Physiol 589.Pt 1 (2011): 221-33.
  37. Grobler L, Collins M and Lambert MI. “Remodelling of skeletal muscle following exercise-induced muscle damage: review article”. Int Sportmed J 5.2 (2004): 67-83.
  38. Heled Y., et al. “CK-MM and ACE genotypes and physiological prediction of the creatine kinase response to exercise”. J Appl Physiol 103.2 (2007): 504-10.
  39. Hyldahl RD and Hubal MJ. “Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise”. Muscle Nerve 49.2 (2014): 155-70.
  40. Howatson G and van Someren KA. “The prevention and treatment of exercise-induced muscle damage”. Sports Med 38.6 (2008): 483-503.
  41. Huang P., et al. “Superoxide dismutase as a target for the selective killing of cancer cells”. Nature 407.6802 (2000): 390-5.
  42. Hubal MJ., et al. “CCL2 and CCR2 polymorphisms are associated with markers of exercise-induced skeletal muscle damage”. J Appl Physiol 108.6 (2010): 1651-8.
  43. Jakobsen MU., et al. “Intake of Total and Subgroups of Fat Minimally Affect the Associations between Selected Single Nucleotide Polymorphisms in the PPARγ Pathway and Changes in Anthropometry among European Adults from Cohorts of the DiOGenes Study”. The Journal of nutrition 146.3 (2016): 603-611.
  44. Jump DB and Clarke SD. “Regulation of gene expression by dietary fat”. Annu Rev Nutr 19 (1999): 63-90.
  45. Laguette MJ., et al. “Sequence variants within the 3'-UTR of the COL5A1 gene alters mRNA stability: implications for musculoskeletal soft tissue injuries”. Matrix Biol 30.5-6 (2011): 338-45.
  46. Larsen SC., et al. “Intake of total and subgroups of fat minimally affect the associations between selected single nucleotide polymorphisms in the PPARγ pathway and changes in anthropometry among European adults from cohorts of the DiOGenes study”. The Journal of Nutrition 146.3 (2016): 603-11.
  47. Longland TM., et al. “Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial”. Am J Clin Nutr 103.3 (2016): 738-46.
  48. Lucía A., et al. “Elite athletes: are the genes the champions?”. Int J Sports Physiol Perform 5.1 (2010): 98-102.
  49. Kicklighter JR., et al. “Visioning Report. A Preferred Path Forward for the Nutrition and Dietetics Profession”. J Acad Nutr Diet 117.1 (2017): 110-127.
  50. Kirk EA., et al. “Human COL5A1 polymorphisms and quadriceps muscle-tendon mechanical stiffness in vivo”. Exp Physiol 101.12 (2016): 1581-1592.
  51. Kriger JW., et al. “Effects of variation in protein and carbohydrate intake on body mass and composition during energy restriction: a meta-regression”. The American Journal of Clinical Nutrition 2 (2006): 260-274.
  52. Kurosaka M and Machida S. “Exercise and skeletal muscle regeneration”. J Phys Fitness Sports Med 1.3 (2012): 537-540.
  53. Macdonald P. “Diversity in translational regulation”. Curr Opin Cell Biol 13.3 (2001): 326-31.
  54. Mackey AL., et al. “Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle”. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 25.6 (2011): 1943-1959.
  55. Marquet LA., et al. “Enhanced Endurance Performance by Periodization of Carbohydrate Intake: "Sleep Low" Strategy”. Med Sci Sports Exerc 48.4 (2016): 663-72.
  56. Martinez Amat A., et al. “Role of alpha-actin in muscle damage of injured athletes in comparison with traditional markers”. Br J Sports Med 41.7 (2007): 442-446.
  57. McHugh MP. “Recent advances in the understanding of the repeated bout effect: the protective effect against muscle damage from a single bout of eccentric exercise”. Scand J Med Sci Sports 13.2 (2003): 88-97.
  58. Morton JP., et al. “The exercise-induced stress response of skeletal muscle, with specific emphasis on humans”. Sports Med 39.8 (2009): 643-62.
  59. Müller M and Kersten S. “Nutrigenomics: goals and strategies”. Nat Rev Genet 4.4 (2003): 315-22.
  60. Naclerio F and Larumbe-Zabala E. “Effects of Whey Protein Alone or as Part of a Multi-ingredient Formulation on Strength, Fat-Free Mass, or Lean Body Mass in Resistance-Trained Individuals: A Meta-analysis”. Sports Med 46.1 (2016): 125-137.
  61. Nascimento M., et al. “Effect of a Nutritional Intervention in Athlete's Body Composition, Eating Behaviour and Nutritional Knowledge: A Comparison between Adults and Adolescents”. Nutrients 8.9 (2016): 535.
  62. Nielsen DE and El-Sohemy A. “Disclosure of genetic information and change in dietary in-take: a randomized controlled trial”. PLoS One 9.11 (2014): e112665.
  63. Ordovas JM and Corella D. “Nutritional genomics”. Annu Rev Genomics Hum Genet 5 (2005): 71-118.
  64. Paulsen G., et al. “Leucocytes, cytokines and satellite cells: what role do they play in muscle damage and regeneration following eccentric exercise?”. Exerc Immunol Rev 18 (2012): 42-97.
  65. Pedersen BK., et al. “Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects”. Pflugers Arch 446.1 (2003): 9-16.
  66. Peterson JM., et al. “Tumor necrosis factor-alpha pro- motes the accumulation of neutrophils and macrophages in skeletal muscle”. J Appl Physiol 101 (2006): 1394-1399.
  67. Pimenta EM., et al. “The ACTN3 genotype in soccer players in response to acute eccentric training”. Eur J Appl Physiol 112.4 (2012): 1495-503.
  68. Prats C., et al. “Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization”. J. Biol. Chem 284 (2009): 15692-15700.
  69. Pruna R., et al. “Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: influence on degree of injury and recovery time”. BMC Musculoskelet Disord 14 (2013): 221.
  70. Richter EA., et al. “Effect of exercise on insulin action in human skeletal muscle”. J Appl Physiol 66.2 (1989): 876-85.
  71. Roig M., et al. “The effects of eccentric versus concentric resistance training on muscle strength and mass in healthy adults: a systematic review with meta-analyses”. Br J Sports Med 43 (2008): 556-568.
  72. Roth SM., et al. ‘Advances in exercise, fitness, and performance genomics in 2011”. Med Sci Sports Exerc 44.5 (2012): 809-17.
  73. Seto JT., et al. “Deficiency of α-actinin-3 is as-sociated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling”. Hum Mol Genet 20.15 (2001): 2914-27.
  74. Schoenfeld BJ. “The mechanisms of muscle hypertrophy and their application to resistance training”. J Strength Cond Res 24.10 (2010): 2857-72.
  75. Schrauwen P., et al. “Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA expression by high-fat diet”. Int J Obes Relat Metab Disord 4 (2011): 449-56.
  76. Sharples AP., et al. “Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake”. Aging Cell 14.4 (2015): 511-23.
  77. Shireman PK., et al. “MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration”. J Leukoc Biol 81.3 (2007): 775-85.
  78. Sprouse C., et al. “SLC30A8 nonsynonymous variant is associated with recovery following exercise and skeletal muscle size and strength”. Diabetes 63.1 (2014): 363-8.
  79. St?pien-S?odkowska M., et al. “The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury”. Biol Sport 1 (2013): 57-60.
  80. Sweeney HL and Stull JT. “Alteration of cross-bridge kinetics by myosin light chain phosphorylation in rabbit skeletal muscle: implications for regulation of actin-myosin interaction”. Proc Natl Acad Sci U S A 87.1 (1990): 414-8.
  81. Szczesna D., et al. “Phosphorylation of the regulatory light chains of myosin affects Ca2+ sensitivity of skeletal muscle contraction”. J Appl Physiol 92.4 (2002): 1661-70.
  82. Tidball JG. “Inflammatory processes in muscle injury and repair”. Am J Physiol Regul Integr Comp Physiol 288.2 (2005): R345-53.
  83. Tipton KD. “Nutrition for acute exercise-induced injuries”. Ann Nutr Metab 57 Suppl 2 (2010): 43-53.
  84. Tipton KD. “Dietary strategies to attenuate muscle loss during recovery from injury”. Nestle Nutr Inst Workshop 75 (2013): 51-61.
  85. Thiebaud RS. “Effects of low-intensity concentric and eccentric exercise combined with blood flow restriction on indices of exercise-induced muscle damage”. Interventional medicine & applied science 5.2 (2013): 53-59.
  86. Verdi Thais. “Sports nutrition: Modulation of gene expression and strategies in physical performance”. Ed Metha 1.3 (2020): 43-63.
  87. Volek JS, Noakes T and Phinney SD. “Rethinking fat as a fuel for endurance exercise”. Eur J Sport Sci 15.1 (2014): 13-20.
  88. Wall BT, Morton JP and van Loon LJ. “Strategies to maintain skeletal muscle mass in the injured athlete: nutritional considerations and exercise mimetics”. Eur J Sport Sci 15.1 (2015): 53-62.
  89. Warren GL., et al. “Chemokine receptor CCR2 involvement in skeletal muscle regeneration”. FASEB J 19.3 (2005): 413-5.
  90. Warren GL., et al. “Physiological role of tumor necrosis factor alpha in traumatic muscle injury”. FASEB J 16.12 (2002): 1630-2.
  91. Willianns AG and Folland JP. “Similarity of polygenic profiles limits the potential for elite human physical performance”. J Physiol 586 (2008): 113-121.
  92. Yahiaoui L., et al. “CC family chemokines directly regulate myoblast responses to skeletal muscle injury”. J Physiol 586.16 (2008): 3991-4004.
  93. Yamin C., et al. “ACE ID genotype affects blood creatine kinase response to eccentric exercise”. J Appl Physiol 103.6 (2007): 2057-2061.
  94. Yang N., et al. “ACTN3 genotype is associated with human elite athletic performance”. Am J Hum Genet 73.3 (2003): 627-31.
  95. Yang N., et al. “ACTN3 genotype is associated with human elite athletic performance”. Am J Hum Genet 73.3 (2003): 627-631.
  96. Yu JG, Carlsson L and Thornell LE. “Evidence for myofibril remodeling as opposed to myofibril damage in human muscles with DOMS: an ultrastructural and immunoelectron microscopic study”. Histochem Cell Biol 121 (2004): 219-227.
  97. Zhou P., et al. “Effects of Dietary Crude Protein Levels and Cysteamine Supplementation on Protein Synthetic and Degradative Signaling in Skeletal Muscle”. PLoS One 10.9 (2015): e0139393.