Sports Medicine

, Volume 41, Issue 10, pp 845–859 | Cite as

Genetic Influences in Sport and Physical Performance

  • Zudin Puthucheary
  • James R. A. Skipworth
  • Jai Rawal
  • Mike Loosemore
  • Ken Van Someren
  • Hugh E. Montgomery
Review Article

Abstract

The common inheritance of approximately 20 000 genes defines each of us as human. However, substantial variation exists between individual human genomes, including ‘replication’ of gene sequences (copy number variation, tandem repeats), or changes in individual base pairs (mutations if <1% frequency and single nucleotide polymorphisms if >1% frequency). A vast array of human phenotypes (e.g. muscle strength, skeletal structure, tendon elasticity, and heart and lung size) influences sports performance, each itself the result of a complex interaction between a myriad of anatomical, biochemical and physiological systems. This article discusses the role for genetic influences in influencing sporting performance and injury, offering specific exemplars where these are known. Many of these preferable genotypes are uncommon, and their combination even rarer. In theory, the chances of an individual having a perfect sporting genotype are much lower than 1 in 20 million — as the number of associated polymorphisms increase, the odds decrease correspondingly. Many recently discovered polymorphisms that may affect sports performance have been described in animal or other human based models, and have been included in this review if they may apply to athletic populations. Muscle performance is heavily influenced by basal muscle mass and its dynamic response to training. Genetic factors account for approximately 5080%of inter-individual variation in lean body mass, with impacts detected on both training-naive’ muscle mass and its growth response. Several cytokines such as interleukin-6 and -15, cilliary neurotrophic factor and insulin-like growth factor (IGF) have myoanabolic effects. Genotype-associated differences in endocrine function, necessary for normal skeletal muscle growth and function, may also be of significance, with complex interactions existing between thyroxine, growth hormone and the downstream regulators of the anabolic pathways (such as IGF-1 and IGF-2). Almost 200 polymorphisms are known to exist in the vitamin D receptor (VDR) gene. VDR genotype is associated with differences in strength in premenopausal women. VDR expression decreases with age and VDR genotype is associated with fatfree mass and strength in elderly men and women. Muscle fibre type determination is complex. Whilst initial composition is likely to be strongly influenced by genetic factors, training has significant effects on fibre shifts. Polymorphisms of the peroxisome proliferator-activated receptor a (PPARa) gene and R577x polymorphism of the ACTN3 gene are both associated with specific fibre compositions. Alterations in cardiac size have been associated with both increased performance and excess cardiovascular mortality. PPARa is a ligand-activated transcription factor that regulates genes involved in fatty acid uptake and oxidation, lipid metabolism and inflammation. Psychology plays an important role in training, competition, tolerance of pain and motivation. However, the role of genetic variation in determining psychological state and responses remains poorly understood; only recently have specific genes been implicated in motivational behaviour and maintenance of exercise. Thyroid hormone receptors exist within the brain and influence both neurogenesis and behaviour. With the current state of knowledge, the field of genetic influences on sports performance remains in its infancy, despite over a decade of research.

Notes

Acknowledgements

The authors have no conflicting interests to declare that are directly relevant to the content of this review. No funding was received for this review. All contributors have met criteria for authorship.

References

  1. 1.
    Goldstein DB, Cavalleri GL. Genomics: understanding human diversity. Nature 2005; 437 (7063): 1241–2PubMedCrossRefGoogle Scholar
  2. 2.
    Montgomery HE, Marshall R, Hemingway H, et al. Human gene for physical performance. Nature 1998; 393 (6682): 221–2PubMedCrossRefGoogle Scholar
  3. 3.
    Williams AG, Dhamrait SS, Wootton PT, et al. Bradykinin receptor gene variant and human physical performance. J Appl Physiol 2004; 96 (3): 938–42PubMedCrossRefGoogle Scholar
  4. 4.
    Woods DR, Montgomery HE. Angiotensin-converting enzyme and genetics at high altitude. High Alt Med Biol 2001; 2 (2): 201–10PubMedCrossRefGoogle Scholar
  5. 5.
    Jones A, Montgomery HE, Woods DR. Human performance: a role for the ACE genotype? Exerc Sport Sci Rev 2002; 30 (4): 184–90PubMedCrossRefGoogle Scholar
  6. 6.
    Wang P, Fedoruk MN, Rupert JL. Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents? Sports Med 2008; 38 (12): 1065–79PubMedCrossRefGoogle Scholar
  7. 7.
    Woods D. Angiotensin-converting enzyme, renin-angiotensin system and human performance. Med Sport Sci 2009; 54: 72–87PubMedCrossRefGoogle Scholar
  8. 8.
    Arden NK, Spector TD. Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res 1997; 12 (12): 2076–81PubMedCrossRefGoogle Scholar
  9. 9.
    Beunen G, Thomis M. Gene powered? Where to go from heritability (h2) in muscle strength and power? Exerc Sport Sci Rev 2004; 32 (4): 148–54PubMedCrossRefGoogle Scholar
  10. 10.
    Bouchard C, Malina RM, Perusse L. Genetics of fitness and physical performance. Champaign (IL): Human Kinetics, 1997Google Scholar
  11. 11.
    Frederiksen H, Bathum L, Worm C, et al. ACE genotype and physical training effects: a randomized study among elderly Danes. Aging Clin Exp Res 2003; 15 (4): 284–91PubMedGoogle Scholar
  12. 12.
    Tiainen K, Sipila S, Alen M, et al. Heritability of maximal isometric muscle strength in older female twins. J Appl Physiol 2004; 96 (1): 173–80PubMedCrossRefGoogle Scholar
  13. 13.
    Maes HH, Beunen GP, Vlietinck RF, et al. Inheritance of physical fitness in 10-yr-old twins and their parents. Med Sci Sports Exerc 1996; 28 (12): 1479–91PubMedCrossRefGoogle Scholar
  14. 14.
    Cupeiro R, Benito PJ, Maffulli N, et al. MCT1 genetic polymorphism influence in high intensity circuit training: a pilot study. J Sci Med Sport 2010; 13 (5): 526–30PubMedCrossRefGoogle Scholar
  15. 15.
    Riechman SE, Balasekaran G, Roth SM, et al. Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J Appl Physiol 2004; 97 (6): 2214–9PubMedCrossRefGoogle Scholar
  16. 16.
    Tsujinaka T, Fujita J, Ebisui C, et al. Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice. J Clin Invest 1996; 97 (1): 244–9PubMedCrossRefGoogle Scholar
  17. 17.
    Goodman MN. Interleukin-6 induces skeletal muscle protein breakdown in rats. Proc Soc Exp Biol Med 1994; 205 (2): 182–5PubMedGoogle Scholar
  18. 18.
    Visser M, Pahor M, Taaffe DR, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle 1. Goldstein DB, Cavalleri GL Genomics: understanding human diversity Nature 2005; 437 (7063): 1241–22Google Scholar
  19. 19.
    Roth SM, Schrager MA, Lee MR, et al. Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not women. J Gerontol A Biol Sci Med Sci 2003; 58 (12): B1085–8CrossRefGoogle Scholar
  20. 20.
    Vergara C, Ramirez B. CNTF, a pleiotropic cytokine: emphasis on its myotrophic role. Brain Res Brain Res Rev 2004; 47 (1-3): 161–73PubMedCrossRefGoogle Scholar
  21. 21.
    Helgren ME, Squinto SP, Davis HL, et al. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell 1994; 76 (3): 493–504PubMedCrossRefGoogle Scholar
  22. 22.
    Guillet C, Auguste P, Mayo W, et al. Ciliary neurotrophic factor is a regulator of muscular strength in aging. J Neurosci 1999; 19 (4): 1257–62PubMedGoogle Scholar
  23. 23.
    Roth SM, Metter EJ, Lee MR, et al. C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women. J Appl Physiol 2003; 95 (4): 1425–30PubMedGoogle Scholar
  24. 24.
    Roth SM, Schrager MA, Ferrell RE, et al. CNTF genotype is associated with muscular strength and quality in humans across the adult age span. J Appl Physiol 2001; 90 (4): 1205–10PubMedGoogle Scholar
  25. 25.
    Schrager MA, Roth SM, Ferrell RE, et al. Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span. J Appl Physiol 2004; 97 (6): 2176–83PubMedCrossRefGoogle Scholar
  26. 26.
    Sayer AA, Syddall H, O’Dell SD, et al. Polymorphism of the IGF2 gene, birth weight and grip strength in adult men. Age Ageing 2002; 31 (6): 468–70PubMedCrossRefGoogle Scholar
  27. 27.
    Weiss RE, Refetoff S. Effect of thyroid hormone on growth: lessons from the syndrome of resistance to thyroid hormone. Endocrinol Metab Clin North Am 1996; 25 (3): 719–30PubMedCrossRefGoogle Scholar
  28. 28.
    Erkintalo M, Bendahan D, Mattéi J-P, et al. Reduced metabolic efficiency of skeletal muscle energetics in hyperthyroid patients evidenced quantitatively by in vivo phosphorus- 31 magnetic resonance spectroscopy. Metabolism 1998; 47 (7): 769–76PubMedCrossRefGoogle Scholar
  29. 29.
    Ceda GP, Fielder PJ, Donovan SM, et al. Regulation of insulin-like growth factor-binding protein expression by thyroid hormone in rat GH3 pituitary tumor cells. Endocrinology 1992; 130 (3): 1483–9PubMedCrossRefGoogle Scholar
  30. 30.
    Crew MD, Spindler SR. Thyroid hormone regulation of the transfected rat growth hormone promoter. J Biol Chem 1986; 261 (11): 5018–22PubMedGoogle Scholar
  31. 31.
    Shapiro LE, Samuels HH, Yaffe BM. Thyroid and glucocorticoid hormones synergistically control growth hormone mRNA in cultured GH1 cells. Proc Natl Acad Sci U S A 1978; 75 (1): 45–9PubMedCrossRefGoogle Scholar
  32. 32.
    Peeters AC, Netea MG, Kullberg BJ, et al. The effect of renin-angiotensin system inhibitors on pro- and antiinflammatory cytokine production. Immunology 1998; 94 (3): 376–9PubMedCrossRefGoogle Scholar
  33. 33.
    van Rossum EF, Koper JW, Huizenga NA, et al. A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels. Diabetes 2002; 51 (10): 3128–34PubMedCrossRefGoogle Scholar
  34. 34.
    van Rossum EF, Voorhoeve PG, te Velde SJ, et al. The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab 2004; 89 (8): 4004–9PubMedCrossRefGoogle Scholar
  35. 35.
    Uitterlinden AG, Fang Y, Van Meurs JB, et al. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004; 338 (2): 143–56PubMedCrossRefGoogle Scholar
  36. 36.
    Baker AR, McDonnell DP, Hughes M, et al. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A 1988; 85 (10): 3294–8PubMedCrossRefGoogle Scholar
  37. 37.
    Norman AW, Nemere I, Zhou LX, et al. 1,25(OH)2- vitamin D3, a steroid hormone that produces biologic effects via both genomic and nongenomic pathways. J Steroid Biochem Mol Biol 1992; 41 (3-8): 231–40PubMedCrossRefGoogle Scholar
  38. 38.
    Walters MR. Newly identified actions of the vitamin D endocrine system. Endocr Rev 1992; 13 (4): 719–64PubMedGoogle Scholar
  39. 39.
    Harant H, Wolff B, Lindley IJ. 1Alpha,25-dihydroxyvitamin D3 decreases DNA binding of nuclear factor kappa B in human fibroblasts. FEBS Lett 1998; 436 (3): 329–34PubMedCrossRefGoogle Scholar
  40. 40.
    Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int 2002; 13 (3): 187–94PubMedCrossRefGoogle Scholar
  41. 41.
    Janssen HC, Samson MM, Verhaar HJ. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 2002; 75 (4): 611–5PubMedGoogle Scholar
  42. 42.
    Endo I, Inoue D, Mitsui T, et al. Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors. Endocrinology 2003; 144 (12): 5138–44PubMedCrossRefGoogle Scholar
  43. 43.
    Holick MF. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone 1995; 17 (2 Suppl.): 107S–11SPubMedCrossRefGoogle Scholar
  44. 44.
    Morelli S, Buitrago C, Vazquez G, et al. Involvement of tyrosine kinase activity in 1alpha,25(OH)2-vitamin D3 signal transduction in skeletal muscle cells. J Biol Chem 2000; 275 (46): 36021–8PubMedCrossRefGoogle Scholar
  45. 45.
    Buitrago CG, Pardo VG, de Boland AR, et al. Activation of RAF-1 through Ras and protein kinase Calpha mediates 1alpha,25(OH)2-vitamin D3 regulation of the mitogenactivated protein kinase pathway in muscle cells. J Biol Chem 2003; 278 (4): 2199–205PubMedCrossRefGoogle Scholar
  46. 46.
    de Boland AR, Morelli S, Boland R. 1,25(OH)2-vitamin D3 signal transduction in chick myoblasts involves phosphatidylcholine hydrolysis. J Biol Chem 1994; 269 (12): 8675–9PubMedGoogle Scholar
  47. 47.
    Buitrago C, Vazquez G, De Boland AR, et al. The vitamin D receptor mediates rapid changes in muscle protein tyrosine phosphorylation induced by 1,25(OH)(2)D(3). Biochem Biophys Res Commun 2001; 289 (5): 1150–6PubMedCrossRefGoogle Scholar
  48. 48.
    Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet 1976; 1 (7960): 626–9PubMedCrossRefGoogle Scholar
  49. 49.
    Yoshikawa S, Nakamura T, Tanabe H, et al. Osteomalacic myopathy. Endocrinol Jpn 1979; 26 Suppl.: 65–72CrossRefGoogle Scholar
  50. 50.
    Russell JA. Osteomalacic myopathy. Muscle Nerve 1994; 17 (6): 578–80PubMedCrossRefGoogle Scholar
  51. 51.
    Ziambaras K, Dagogo-Jack S. Reversible muscle weakness in patients with vitamin D deficiency. West J Med 1997; 167 (6): 435–9PubMedGoogle Scholar
  52. 52.
    Birge SJ, Haddad JG. 25-hydroxycholecalciferol stimulation of muscle metabolism. J Clin Invest 1975; 56 (5): 1100–7PubMedCrossRefGoogle Scholar
  53. 53.
    Bischoff HA, Stahelin HB, Dick W, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 2003; 18 (2): 343–51PubMedCrossRefGoogle Scholar
  54. 54.
    Dukas L, Bischoff HA, Lindpaintner LS, et al. Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimumcalcium intake of more than 500mg daily. J Am Geriatr Soc 2004; 52 (2): 230–6PubMedCrossRefGoogle Scholar
  55. 55.
    Bunout D, Barrera G, Leiva L, et al. Effects of vitamin D supplementation and exercise training on physical performance in Chilean vitamin D deficient elderly subjects. Exp Gerontol 2006; 41 (8): 746–52PubMedCrossRefGoogle Scholar
  56. 56.
    Fang Y, van Meurs JB, d’Alesio A, et al. Promoter and 3’-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am J Hum Genet 2005; 77 (5): 807–23PubMedCrossRefGoogle Scholar
  57. 57.
    Crofts LA, Hancock MS, Morrison NA, et al. Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts. Proc Natl Acad Sci U S A 1998; 95 (18): 10529–34PubMedCrossRefGoogle Scholar
  58. 58.
    Faraco JH, Morrison NA, Baker A, et al. ApaI dimorphism at the human vitamin D receptor gene locus. Nucleic Acids Res 1989; 17 (5): 2150PubMedCrossRefGoogle Scholar
  59. 59.
    Morrison NA, Yeoman R, Kelly PJ, et al. Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci U S A 1992; 89 (15): 6665–9PubMedCrossRefGoogle Scholar
  60. 60.
    Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994; 367 (6460): 284–7PubMedCrossRefGoogle Scholar
  61. 61.
    Ye WZ, Reis AF, Velho G. Identification of a novel Tru9 I polymorphism in the human vitamin D receptor gene. J Hum Genet 2000; 45 (1): 56–7PubMedCrossRefGoogle Scholar
  62. 62.
    Arai H, Miyamoto K, Taketani Y, et al. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 1997; 12 (6): 915–21PubMedCrossRefGoogle Scholar
  63. 63.
    McCullough ML, Stevens VL, Diver WR, et al. Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study. Breast Cancer Res 2007; 9 (1): R9CrossRefGoogle Scholar
  64. 64.
    Bahat G, Saka B, Erten N, et al. BsmI polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men. Aging Clin Exp Res 2010; 22 (3): 198–205PubMedGoogle Scholar
  65. 65.
    Grundberg E, Brandstrom H, Ribom EL, et al. Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 2004; 150 (3): 323–8PubMedCrossRefGoogle Scholar
  66. 66.
    Bischoff-Ferrari HA, Borchers M, Gudat F, et al. Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 2004; 19 (2): 265–9PubMedCrossRefGoogle Scholar
  67. 67.
    Roth SM, Zmuda JM, Cauley JA, et al. Vitamin Dreceptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci 2004; 59 (1): 10–5PubMedCrossRefGoogle Scholar
  68. 68.
    Geusens P, Vandevyver C, Vanhoof J, et al. Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res 1997; 12 (12): 2082–8PubMedCrossRefGoogle Scholar
  69. 69.
    Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 2003; 88 (12): 5766–72PubMedCrossRefGoogle Scholar
  70. 70.
    Flicker L, Mead K, MacInnis RJ, et al. Serum vitamin D and falls in older women in residential care in Australia. J Am Geriatr Soc 2003; 51 (11): 1533–8PubMedCrossRefGoogle Scholar
  71. 71.
    Tajima O, Ashizawa N, Ishii T, et al. Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism. J Appl Physiol 2000; 88 (4): 1271–6PubMedGoogle Scholar
  72. 72.
    Nakamura O, Ishii T, Ando Y, et al. Potential role of vitaminDreceptor gene polymorphism in determining bone phenotype in young male athletes. J Appl Physiol 2002; 93 (6): 1973–9PubMedGoogle Scholar
  73. 73.
    Rabon-Stith KM, Hagberg JM, Phares DA, et al. Vitamin Dreceptor FokI genotype influences bone mineral density response to strength training, but not aerobic training. Exp Physiol 2005; 90 (4): 653–61PubMedCrossRefGoogle Scholar
  74. 74.
    Diogenes ME, Bezerra FF, Cabello GM, et al. Vitamin D receptor gene FokI polymorphisms influence bone mass in adolescent football (soccer) players. Eur J Appl Physiol 2010; 108 (1): 31–8PubMedCrossRefGoogle Scholar
  75. 75.
    Chatzipapas C, Boikos S, Drosos GI, et al. Polymorphisms of the vitamin D receptor gene and stress fractures. Horm Metab Res 2009; 41 (8): 635–40PubMedCrossRefGoogle Scholar
  76. 76.
    Simoneau JA, Bouchard C. Human variation in skeletal muscle fiber-type proportion and enzyme activities. Am J Physiol 1989; 257 (4Pt1): E567–72Google Scholar
  77. 77.
    Simoneau JA, Bouchard C. Genetic determinism of fiber type proportion in human skeletal muscle. FASEB J 1995; 9 (11): 1091–5PubMedGoogle Scholar
  78. 78.
    Staron RS, Malicky ES, Malicky ES, et al. Muscle hypertrophy and fast fiber type conversions in heavy resistancetrained women. Eur J Appl Physiol Occup Physiol 1990; 60 (1): 71–9PubMedCrossRefGoogle Scholar
  79. 79.
    Williamson DL, Gallagher PM, Carroll CC, et al. Reduction in hybrid single muscle fiber proportions with resistance training in humans. J Appl Physiol 2001; 91 (5): 1955–61PubMedGoogle Scholar
  80. 80.
    Booth FW, Thomason DB. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. Physiol Rev 1991; 71 (2): 541–85PubMedGoogle Scholar
  81. 81.
    Gosker HR, van Mameren H, van Dijk PJ, et al. Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease. Eur Respir J 2002; 19 (4): 617–25PubMedCrossRefGoogle Scholar
  82. 82.
    Bouchard C, Simoneau JA, Simoneau JA, et al. Genetic effects in human skeletal muscle fiber type distribution and enzyme activities. Can J Physiol Pharmacol 1986; 64 (9): 1245–51PubMedCrossRefGoogle Scholar
  83. 83.
    Ahmetov II, Mozhayskaya IA, Flavell DM, et al. PPAR alpha gene variation and physical performance in Russian athletes. Eur J Appl Physiol 2006; 97 (1): 103–8PubMedCrossRefGoogle Scholar
  84. 84.
    Vincent B, De Bock K, Ramaekers M, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics 2007; 32 (1): 58–63Google Scholar
  85. 85.
    Ahmetov II, Druzhevskaya AM, Astratenkova IV, et al. The ACTN3 R577X polymorphism in Russian endurance athletes. Br J Sports Med 2010; 44 (9): 649–52PubMedCrossRefGoogle Scholar
  86. 86.
    Hanson ED, Ludlow AT, Sheaff AK, et al. ACTN3 genotype does not influence muscle power. Int J Sports Med 2010; 31 (11): 834–8PubMedCrossRefGoogle Scholar
  87. 87.
    Ruiz JR, Fernandez Del Valle M, Verde Z, et al. ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players. Scand J Med Sci Sports. Epub 2010 Jun 18Google Scholar
  88. 88.
    Santiago C, Rodriguez-Romo G, Gomez-Gallego F, et al. Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young, non-athletic adults? Scand J Med Sci Sports 2010; 20 (5): 771–8PubMedCrossRefGoogle Scholar
  89. 89.
    Zempo H, Tanabe K, Murakami H, et al. ACTN3 polymorphism affects thigh muscle area. Int J Sports Med 2010; 31 (2): 138–42PubMedCrossRefGoogle Scholar
  90. 90.
    Rodriguez-Romo G, Ruiz JR, Santiago C, et al. Does the ACE I/Dpolymorphism, alone or in combination with the ACTN3 R577X polymorphism, influence muscle power phenotypes in young, non-athletic adults? Eur J Appl Physiol 2010; 110 (6): 1099–106PubMedCrossRefGoogle Scholar
  91. 91.
    Ahmetov II, Hakimullina AM, Popov DV, et al. Association of the VEGFR2 gene His472Gln polymorphism with endurance-related phenotypes. Eur J Appl Physiol 2009; 107 (1): 95–103PubMedCrossRefGoogle Scholar
  92. 92.
    Jarvinen TA, Jozsa L, Kannus P, et al. Organization and distribution of intramuscular connective tissue in normal and immobilized skeletal muscles: an immunohistochemical, polarization and scanning electron microscopic study. J Muscle Res Cell Motil 2002; 23 (3): 245–54PubMedCrossRefGoogle Scholar
  93. 93.
    Takala TE VP. Biochemical composition of muscle extracellular matrix: the effect of loading. Scand J Med Sci Sports 2000; 10 (6): 321–5PubMedCrossRefGoogle Scholar
  94. 94.
    Van Pottelbergh I, Nuytinck L, De Paepe A, et al. Association of the type I collagen alpha1 Sp1 polymorphism, bone density and upper limb muscle strength in community- dwelling elderly men. Osteoporos Int 2001; 12 (10): 895–901PubMedCrossRefGoogle Scholar
  95. 95.
    Kiel DP, Myers RH, Cupples LA, et al. The BsmI vitamin Dreceptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density. J Bone Miner Res 1997; 12 (7): 1049–57PubMedCrossRefGoogle Scholar
  96. 96.
    Jones BH, Thacker SB, Gilchrist J, et al. Prevention of lower extremity stress fractures in athletes and soldiers: a systematic review. Epidemiol Rev 2002; 24 (2): 228–47PubMedCrossRefGoogle Scholar
  97. 97.
    Smith DM, Nance WE, Kang KW, et al. Genetic factors in determining bone mass. J Clin Invest 1973; 52 (11): 2800–8PubMedCrossRefGoogle Scholar
  98. 98.
    Pocock NA, Eisman JA, Hopper JL, et al. Genetic determinants of bone mass in adults: a twin study. J Clin Invest 1987; 80 (3): 706–10PubMedCrossRefGoogle Scholar
  99. 99.
    Torgerson DJ, Campbell MK, Thomas RE, et al. Prediction of perimenopausal fractures by bone mineral density and other risk factors. J Bone Miner Res 1996; 11 (2): 293–7PubMedCrossRefGoogle Scholar
  100. 100.
    Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women: Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332 (12): 767–73PubMedCrossRefGoogle Scholar
  101. 101.
    Zhao L, Zhao M, Fang Q. Spironolactone ameliorates rat pulmonary fibrosis induced by bleomycin A5 [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi 1998; 21 (5): 300–2PubMedGoogle Scholar
  102. 102.
    Hosoi T, Miyao M, Inoue S, et al. Association study of parathyroid hormone gene polymorphism and bone mineral density in Japanese postmenopausal women. Calcif Tissue Int 1999; 64 (3): 205–8PubMedCrossRefGoogle Scholar
  103. 103.
    Van Pottelbergh I, Goemaere S, Kaufman JM. Bioavailable estradiol and an aromatase gene polymorphism are determinants of bone mineral density changes in men over 70 years of age. J Clin Endocrinol Metab 2003; 88 (7): 3075–81PubMedCrossRefGoogle Scholar
  104. 104.
    Salmen T, Heikkinen AM, Mahonen A, et al. Relation of aromatase gene polymorphism and hormone replacement therapy to serum estradiol levels, bone mineral density, and fracture risk in early postmenopausal women. Ann Med 2003; 35 (4): 282–8PubMedCrossRefGoogle Scholar
  105. 105.
    Kobayashi S, Inoue S, Hosoi T, et al. Association of bone mineral density with polymorphism of the estrogen receptor gene. J Bone Miner Res 1996; 11 (3): 306–11PubMedCrossRefGoogle Scholar
  106. 106.
    Mizunuma H, Hosoi T, Okano H, et al. Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and postmenopausal women. Bone 1997; 21 (5): 379–83PubMedCrossRefGoogle Scholar
  107. 107.
    Feng D IH, Yamamoto S, Hosoi T, et al. Association between bone loss and promoter polymorphism in the IL-6 gene in elderly Japanese women with hip fracture. J Bone Miner Metab 2003; 21 (4): 225–8PubMedGoogle Scholar
  108. 108.
    Liu XH LY, Jiang DK, Li YM, et al.No evidence for linkage and/or association of human alpha2-HS glycoprotein gene with bone mineral density variation in Chinese nuclear families. Calcif Tissue Int 2003; 73 (3): 244–50PubMedCrossRefGoogle Scholar
  109. 109.
    Sainz J, Van Tornout JM, Loro ML, et al. Vitamin Dreceptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent. N Engl J Med 1997; 337 (2): 77–82PubMedCrossRefGoogle Scholar
  110. 110.
    Ferrari S, Rizzoli R, Manen D, et al. Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3’-end region polymorphisms. J Bone Miner Res 1998; 13 (6): 925–30PubMedCrossRefGoogle Scholar
  111. 111.
    Cooper GS, Umbach DM. Are vitamin D receptor polymorphisms associated with bone mineral density? A metaanalysis. J Bone Miner Res 1996; 11 (12): 1841–9PubMedCrossRefGoogle Scholar
  112. 112.
    Ferrari SL, Rizzoli R. Gene variants for osteoporosis and their pleiotropic effects in aging. Mol Aspects Med 2005; 26 (3): 145–67PubMedCrossRefGoogle Scholar
  113. 113.
    Thakkinstian A, D’Este C, Attia J. Haplotype analysis of VDR gene polymorphisms: a meta-analysis. Osteoporos Int 2004; 15 (9): 729–34PubMedCrossRefGoogle Scholar
  114. 114.
    Thakkinstian A, D’Este C, Eisman J, et al. Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res 2004; 19 (3): 419–28PubMedCrossRefGoogle Scholar
  115. 115.
    Gong G, Stern HS, Cheng SC, et al. The association of bone mineral density with vitamin D receptor gene polymorphisms. Osteoporos Int 1999; 9 (1): 55–64PubMedCrossRefGoogle Scholar
  116. 116.
    Zofkova I. Hormonal aspects of the muscle-bone unit. Physiol Res 2008; 57 Suppl.1: S159–69Google Scholar
  117. 117.
    Young LE, Rogers K, Wood JL. Left ventricular size and systolic function in thoroughbred racehorses and their relationships to race performance. J Appl Physiol 2005; 99 (4): 1278–85PubMedCrossRefGoogle Scholar
  118. 118.
    Koren MJ, Devereux RB, Casale PN, et al. Relation of left ventricularmass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991; 114 (5): 345–52PubMedGoogle Scholar
  119. 119.
    Levy D, Garrison RJ, Savage DD, et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322 (22): 1561–6PubMedCrossRefGoogle Scholar
  120. 120.
    Vakili BA, Okin PM, Devereux RB. Prognostic implications of left ventricular hypertrophy. Am Heart J 2001; 141 (3): 334–41PubMedCrossRefGoogle Scholar
  121. 121.
    Buhl R, Ersbll AK, Eriksen L, et al. Changes over time in echocardiographic measurements in young standardbred racehorses undergoing training and racing and association with racing performance. J Am Vet Med Assoc 2005; 226 (11): 1881–7PubMedCrossRefGoogle Scholar
  122. 122.
    Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347 (6294): 645–50PubMedCrossRefGoogle Scholar
  123. 123.
    Fruchart JC, Duriez P, Staels B. Peroxisome proliferatoractivated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol 1999; 10 (3): 245–57PubMedCrossRefGoogle Scholar
  124. 124.
    Sack MN, Rader TA, Park S, et al. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 1996; 94 (11): 2837–42PubMedCrossRefGoogle Scholar
  125. 125.
    Barger PM, Brandt JM, Leone TC, et al. Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest 2000; 105 (12): 1723–30PubMedCrossRefGoogle Scholar
  126. 126.
    Binas B, Danneberg H, McWhir J, et al. Requirement for the heart-type fatty acid binding protein in cardiac fatty acid utilization. FASEB J 1999; 13 (8): 805–12PubMedGoogle Scholar
  127. 127.
    Chiu HC, Kovacs A, Ford DA, et al. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 2001; 107 (7): 813–22PubMedCrossRefGoogle Scholar
  128. 128.
    Jamshidi Y, Montgomery HE, Hense HW, et al. Peroxisome proliferator: activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation 2002; 105 (8): 950–5PubMedCrossRefGoogle Scholar
  129. 129.
    Schunkert H, Hengstenberg C, Holmer SR, et al. Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. Circulation 1999; 99 (17): 2255–60PubMedCrossRefGoogle Scholar
  130. 130.
    Reinhard C, Meyer B, Fuchs H, et al. Genomewide linkage analysis identifies novel genetic loci for lung function in mice. Am J Respir Crit Care Med 2005; 171 (8): 880–8PubMedCrossRefGoogle Scholar
  131. 131.
    Lewiiter FI, Tager IB, McGue M, et al. Genetic and environmental determinants of level of pulmonary function. Am J Epidemiol 1984; 120 (4): 518–30Google Scholar
  132. 132.
    Chen Y, Rennie DC, Lockinger LA, et al. Major genetic effect on forced vital capacity: the Humboldt Family Study. Genet Epidemiol 1997; 14 (1): 63–76PubMedCrossRefGoogle Scholar
  133. 133.
    Coultas DB, Hanis CL, Howard CA, et al. Heritability of ventilatory function in smoking and nonsmoking New Mexico Hispanics. Am Rev Respir Dis 1991; 144 (4): 770–5PubMedCrossRefGoogle Scholar
  134. 134.
    Joost O, Wilk JB, Adrienne Cupples L, et al. Genetic loci influencing lung function: a genomewide scan in the Framingham Study. Am J Respir Crit Care Med 2002; 165 (6): 795–9PubMedGoogle Scholar
  135. 135.
    Palmer LJ, Knuiman MW, Divitini ML, et al. Familial aggregation and heritability of adult lung function: results from the Busselton Health Study. Eur Respir J 2001; 17 (4): 696–702PubMedCrossRefGoogle Scholar
  136. 136.
    Dempsey JA, Johnson BD, Saupe KW. Adaptations and limitations in the pulmonary system during exercise. Chest 1990; 97 (3 Suppl.): 81S–7SPubMedCrossRefGoogle Scholar
  137. 137.
    Dempsey JA, Wagner PD. Exercise-induced arterial hypoxemia. J Appl Physiol 1999; 87 (6): 1997–2006PubMedGoogle Scholar
  138. 138.
    Gavin TP, Stager JM. The effect of exercise modality on exercise-induced hypoxemia. Respir Physiol 1999; 115 (3): 317–23PubMedCrossRefGoogle Scholar
  139. 139.
    Nielsen HB. Arterial desaturation during exercise in man: implication for O-2 uptake and work capacity. Scand JMed Sci Sports 2003; 13 (6): 339–58CrossRefGoogle Scholar
  140. 140.
    Holmberg HC, Rosdahl H, Svedenhag J. Lung function, arterial saturation and oxygen uptake in elite cross country skiers: influence of exercise mode. Scand J Med Sci Sports 2007; 17 (4): 437–44PubMedGoogle Scholar
  141. 141.
    Doherty M, Dimitriou L. Comparison of lung Vol. in Greek swimmers, land based athletes, and sedentary controls using allometric scaling. Br J Sports Med 1997; 31 (4): 337–41PubMedCrossRefGoogle Scholar
  142. 142.
    Lippi G, Longo UG, Maffulli N. Genetics and sports. Br Med Bull 2010; 93: 27–47PubMedCrossRefGoogle Scholar
  143. 143.
    Wilcoxon JS, Nadolski GJ, Samarut J, et al. Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res 2007; 177 (1): 109–16PubMedCrossRefGoogle Scholar
  144. 144.
    Bryan A, Hutchison KE, Seals DR, et al. A transdisciplinary model integrating genetic, physiological, and psychological correlates of voluntary exercise. Health Psychol 2007; 26 (1): 30–9PubMedCrossRefGoogle Scholar
  145. 145.
    Maliuchenko NV, Sysoeva OV, Vediakov AM, et al. Effect of 5HTT genetic polymorphism on aggression in athletes [in Russian]. Zh Vyssh Nerv Deiat Im I P Pavlova 2007; 57 (3): 276–81PubMedGoogle Scholar
  146. 146.
    Tschenett A, Singewald N, Carli M, et al. Reduced anxiety and improved stress coping ability in mice lacking NPY-Y2 receptors. Eur J Neurosci 2003; 18 (1): 143–8PubMedCrossRefGoogle Scholar
  147. 147.
    Gerlai R, Roder JC, Hampson DR. Altered spatial learning and memory in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. Behav Neurosci 1998; 112 (3): 525–32PubMedCrossRefGoogle Scholar
  148. 148.
    Gimenez-Llort L, Masino SA, Diao L, et al. Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly. Synapse 2005; 57 (1): 8–16PubMedCrossRefGoogle Scholar
  149. 149.
    Trejo JL, Llorens-Martin MV, Torres-Aleman I. The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci 2008; 37 (2): 402–11PubMedCrossRefGoogle Scholar
  150. 150.
    Mogil JS, Lichtensteiger CA, Wilson SG. The effect of genotype on sensitivity to inflammatory nociception: characterization of resistant (A/J) and sensitive (C57BL/6J) inbred mouse strains. Pain 1998; 76 (1-2): 115–25PubMedCrossRefGoogle Scholar
  151. 151.
    Foulkes T, Wood JN. Pain genes. PLoS Genet 2008; 4 (7): e1000086CrossRefGoogle Scholar
  152. 152.
    Priest BT, Murphy BA, Lindia JA, et al. Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior. Proc Natl Acad Sci U S A 2005; 102 (26): 9382–7PubMedCrossRefGoogle Scholar
  153. 153.
    Nassar MA, Stirling LC, Forlani G, et al. Nociceptorspecific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A 2004; 101 (34): 12706–11PubMedCrossRefGoogle Scholar
  154. 154.
    Zimmermann K, Leffler A, Babes A, et al. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature 2007; 447 (7146): 855–8PubMedCrossRefGoogle Scholar
  155. 155.
    Cox JJ, Reimann F, Nicholas AK, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006; 444 (7121): 894–8PubMedCrossRefGoogle Scholar
  156. 156.
    Collins M, Xenophontos SL, Cariolou MA, et al. The ACE gene and endurance performance during the South African Ironman Triathlons. Med Sci Sports Exerc 2004; 36 (8): 1314–20PubMedCrossRefGoogle Scholar
  157. 157.
    Costa A, Silva A, Garrido N, et al. Association between ACE D allele and elite short distance swimming. Eur J Appl Physiol 2009; 106 (6): 785–90PubMedCrossRefGoogle Scholar
  158. 158.
    Gayagay G, Yu B, Hambly B, et al. Elite endurance athletes and the ACE I allele: the role of genes in athletic performance. Hum Genet 1998; 103 (1): 48–50PubMedCrossRefGoogle Scholar
  159. 159.
    Jones A, Woods DR. Skeletal muscle RAS and exercise performance. Int J Biochem Cell Biol 2003; 35 (6): 855–66PubMedCrossRefGoogle Scholar
  160. 160.
    Williams AG, Rayson MP, Jubb M, et al. The ACE gene and muscle performance [letter]. Nature 2000; 403 (6770): 614PubMedGoogle Scholar
  161. 161.
    Woods DR, Humphries SE, Montgomery HE. The ACE I/D polymorphism and human physical performance. Trends Endocrinol Metab 2000; 11 (10): 416–20PubMedCrossRefGoogle Scholar
  162. 162.
    Moran CN, Yang N, Yang N, et al. Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks. Eur J Hum Genet 2006; 15 (1): 88–93PubMedCrossRefGoogle Scholar
  163. 163.
    Yang N, MacArthur DG, Gulbin JP, et al. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 2003; 73 (3): 627–31PubMedCrossRefGoogle Scholar
  164. 164.
    Ahmetov II, Williams AG, Popov DV, et al. The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes. Hum Genet 2009; 126 (6): 751–61PubMedCrossRefGoogle Scholar
  165. 165.
    Williams AG, Folland JP. Similarity of polygenic profiles limits the potential for elite human physical performance. J Physiol 2008; 586 (1): 113–21PubMedCrossRefGoogle Scholar
  166. 166.
    Kannus P, Natri A. Etiology and pathophysiology of tendon ruptures in sports. Scand J Med Sci Sports 1997; 7 (2): 107–12PubMedCrossRefGoogle Scholar
  167. 167.
    Gwilym SE, Watkins B, Cooper CD, et al. Genetic influences in the progression of tears of the rotator cuff. J Bone Joint Surg Br 2009; 91 (7): 915–7PubMedCrossRefGoogle Scholar
  168. 168.
    Harvie P, Ostlere SJ, Teh J, et al. Genetic influences in the aetiology of tears of the rotator cuff: sibling risk of a fullthickness tear. J Bone Joint Surg Br 2004; 86 (5): 696–700PubMedCrossRefGoogle Scholar
  169. 169.
    Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am 2005; 87 (1): 187–202PubMedCrossRefGoogle Scholar
  170. 170.
    Mokone GG, Schwellnus MP, Noakes TD, et al. The COL5A1 gene and Achilles tendon pathology. Scand J Med Sci Sports 2006; 16 (1): 19–26PubMedCrossRefGoogle Scholar
  171. 171.
    Mokone GG, Gajjar M, September AV, et al. The guaninethymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with achilles tendon injuries. Am J Sports Med 2005; 33 (7): 1016–21PubMedCrossRefGoogle Scholar
  172. 172.
    Waggett AD, Ralphs JR, Kwan AP, et al. Characterization of collagens and proteoglycans at the insertion of the human Achilles tendon. Matrix Biol 1998; 16 (8): 457–70PubMedCrossRefGoogle Scholar
  173. 173.
    Vogel KG. What happens when tendons bend and twist? Proteoglycans. J Musculoskelet Neuronal Interact, 2004; 4 (2): 202–3PubMedGoogle Scholar
  174. 174.
    Lysholm J, Wiklander J. Injuries in runners. Am J Sports Med 1987; 15 (2): 168–71PubMedCrossRefGoogle Scholar
  175. 175.
    Knobloch K, Yoon U, Vogt PM. Acute and overuse injuries correlated to hours of training in master running athletes. Foot Ankle Int 2008; 29 (7): 671–6PubMedCrossRefGoogle Scholar
  176. 176.
    Jones GC, Corps AN, Pennington CJ, et al. Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon. Arthritis Rheum 2006; 54 (3): 832–42PubMedCrossRefGoogle Scholar
  177. 177.
    Karousou E, Ronga M, Vigetti D, et al. Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture. Clin Orthop Relat Res 2008; 466 (7): 1577–82PubMedCrossRefGoogle Scholar
  178. 178.
    Corps AN, Jones GC, Harrall RL, et al. The regulation of aggrecanase ADAMTS-4 expression in human Achilles tendon and tendon-derived cells. Matrix Biol 2008; 27 (5): 393–401PubMedCrossRefGoogle Scholar
  179. 179.
    Pufe T, Petersen WJ, Mentlein R, et al. The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease. Scand JMed Sci Sports 2005; 15 (4): 211–22CrossRefGoogle Scholar
  180. 180.
    Petersen W, Pufe T, Zantop T, et al. Expression of VEGFR-1 and VEGFR-2 in degenerative Achilles tendons. Clin Orthop Relat Res 2004 (420): 286–91PubMedCrossRefGoogle Scholar
  181. 181.
    Posthumus M, September AV, Schwellnus MP, et al. Investigation of the Sp1-binding site polymorphism within the COL1A1 gene in participants with Achilles tendon injuries and controls. J Sci Med Sport 2009; 12 (1): 184–9PubMedCrossRefGoogle Scholar
  182. 182.
    Bray MS, Hagberg JM, Perusse L, et al. The human gene map for performance and health-related fitness phenotypes: the 2006–2007 update. Med Sci Sports Exerc 2009; 41 (1): 35–73PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Zudin Puthucheary
    • 1
  • James R. A. Skipworth
    • 1
  • Jai Rawal
    • 1
  • Mike Loosemore
    • 2
  • Ken Van Someren
    • 2
  • Hugh E. Montgomery
    • 1
  1. 1.UCL Institute for Human Health and PerformanceArchway, LondonUK
  2. 2.English Institute of Sport, Bisham Abbey National Sports CentreMarlow, BuckinghamshireUK

Personalised recommendations