Genetic Aspects of Muscular Strength and Size

  • Monica J. Hubal
  • Maria L. Urso
  • Priscilla M. Clarkson
Chapter
First Online:
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

This chapter reviews common genetic variants (single nucleotide polymorphisms; SNPs) that reportedly influence baseline and resistance training induced changes in skeletal muscle size and strength. Genetic variants associated with strength and size have been found in a structural gene (alpha-actinin 3), growth factor genes (e.g., insulin-like growth factor 1 and myostatin), and inflammatory genes (e.g., interleukin 6 and tumor necrosis factor alpha). The biological basis for each of these three categories of genes is discussed and SNP association studies are highlighted. In most cases, single variants and single genes account for low percentages of trait variability on their own and few interactions between multiple genetic variations have been investigated to date. Future studies would benefit from emerging high throughput genotyping methods to enable comparisons across multiple genes, which can enhance identification of multiple gene/loci associations. Potential practical applications of exercise/muscle genomics include the ability to identify individuals with gene variants associated with increased athletic performance, optimization of training and rehabilitation strategies via individually tailored programs, and enhanced musculoskeletal health over the lifespan through the development of gene and pathway targeted therapeutics.

Keywords

Hypertrophy Resistance training Genetic variants Genotype association Single nucleotide polymorphism Adaptation Fiber type Alpha-actinin 3 Protein synthesis Growth factors Phosphatidylinositol-3-kinase Protein kinase B Mammalian target of rapamycin Insulin-like growth factor Mechano growth factor Myostatin Inflammatory factors Cytokines Tumor necrosis factor alpha Interleukin-6 Interleukin-15 Exercise genomics Polygenic traits Genome wide association study Next generation sequencing Genetic testing Angiotensin converting enzyme Protein phosphatase 3 regulatory subunit B Insulin-like growth factor binding protein 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Baechle T, Earle R, editors. Essentials of Strength Training and Conditioning: Human Kinetics, 2008.Google Scholar
  2. 2.
    Sale DG. Neural adaptation to resistance training. Med Sci Sports Exerc. 1988;20 (5 Suppl):S135–45.PubMedGoogle Scholar
  3. 3.
    Hubal MJ, Gordish-Dressman H, Thompson PD, Price TB, Hoffman EP, Angelopoulos TJ, et al. Variability in muscle size and strength gain after unilateral resistance training. Med Sci Sports Exerc. 2005;37(6):964–72.PubMedGoogle Scholar
  4. 4.
    Thomis MA, Beunen GP, Van Leemputte M, Maes HH, Blimkie CJ, Claessens AL, et al. Inheritance of static and dynamic arm strength and some of its determinants. Acta Physiol Scand. 1998;163(1):59–71.PubMedGoogle Scholar
  5. 5.
    Thomis MA, Beunen GP, Maes HH, Blimkie CJ, Van Leemputte M, Claessens AL, et al. Strength training: importance of genetic factors. Med Sci Sports Exerc. 1998;30(5):724–31.PubMedGoogle Scholar
  6. 6.
    Perusse L, Lortie G, Leblanc C, Tremblay A, Theriault G, Bouchard C. Genetic and environmental sources of variation in physical fitness. Ann Hum Biol. 1987;14(5):425–34.PubMedGoogle Scholar
  7. 7.
    Seeman E, Hopper JL, Young NR, Formica C, Goss P, Tsalamandris C. Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study. Am J Physiol. 1996;270(2 Pt 1):E320–7.PubMedGoogle Scholar
  8. 8.
    Nguyen TV, Howard GM, Kelly PJ, Eisman JA. Bone mass, lean mass, and fat mass: same genes or same environments? Am J Epidemiol. 1998;147(1):3–16.PubMedGoogle Scholar
  9. 9.
    Forbes GB, Sauer EP, Weitkamp LR. Lean body mass in twins. Metabolism. 1995;44(11):1442–6.PubMedGoogle Scholar
  10. 10.
    Calvo M, Rodas G, Vallejo M, Estruch A, Arcas A, Javierre C, et al. Heritability of explosive power and anaerobic capacity in humans. Eur J Appl Physiol. 2002;86(3):218–25.PubMedGoogle Scholar
  11. 11.
    Baar K, Nader G, Bodine S. Resistance exercise, muscle loading/unloading and the control of muscle mass. Essays Biochem. 2006;42:61–74.PubMedGoogle Scholar
  12. 12.
    Weiss A, Leinwand LA. The mammalian myosin heavy chain gene family. Annu Rev Cell Dev Biol. 1996;12:417–39.PubMedGoogle Scholar
  13. 13.
    Delmonico MJ, Kostek MC, Doldo NA, Hand BD, Walsh S, Conway JM, et al. Alpha-actinin-3 (ACTN3) R577X polymorphism influences knee extensor peak power response to strength training in older men and women. J Gerontol A Biol Sci Med Sci. 2007;62(2):206–12.PubMedGoogle Scholar
  14. 14.
    MacArthur DG, North KN. A gene for speed? The evolution and function of alpha-actinin-3. Bioessays. 2004;26(7):786–95.PubMedGoogle Scholar
  15. 15.
    MacArthur DG, North KN. ACTN3: A genetic influence on muscle function and athletic performance. Exerc Sport Sci Rev. 2007;35(1):30–4.PubMedGoogle Scholar
  16. 16.
    Norman B, Esbjornsson M, Rundqvist H, Osterlund T, von Walden F, Tesch PA. Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol. 2009;106(3):959–65.PubMedGoogle Scholar
  17. 17.
    Clarkson PM, Devaney JM, Gordish-Dressman H, Thompson PD, Hubal MJ, Urso M, et al. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol. 2005;99(1):154–63.PubMedGoogle Scholar
  18. 18.
    Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, et al. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet. 2003;73(3):627–31.PubMedGoogle Scholar
  19. 19.
    Vincent B, De Bock K, Ramaekers M, Van den Eede E, Van Leemputte M, Hespel P, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics. 2007;32(1):58–63.PubMedGoogle Scholar
  20. 20.
    MacArthur DG, Seto JT, Chan S, Quinlan KG, Raftery JM, Turner N, et al. An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance. Hum Mol Genet. 2008;17(8):1076–86.PubMedGoogle Scholar
  21. 21.
    MacArthur DG, Seto JT, Raftery JM, Quinlan KG, Huttley GA, Hook JW, et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet. 2007;39(10):1261–5.PubMedGoogle Scholar
  22. 22.
    Chan S, Seto JT, MacArthur DG, Yang N, North KN, Head SI. A gene for speed: contractile properties of isolated whole EDL muscle from an alpha-actinin-3 knockout mouse. Am J Physiol Cell Physiol. 2008;295(4):C897–904.PubMedGoogle Scholar
  23. 23.
    Friden J. Changes in human skeletal muscle induced by long-term eccentric exercise. Cell Tissue Res. 1984;236(2):365–72.PubMedGoogle Scholar
  24. 24.
    Friden J, Sjostrom M, Ekblom B. Myofibrillar damage following intense eccentric exercise in man. Int J Sports Med. 1983;4(3):170–6.PubMedGoogle Scholar
  25. 25.
    Clarkson PM, Hoffman EP, Zambraski E, Gordish-Dressman H, Kearns A, Hubal M, et al. ACTN3 and MLCK genotype associations with exertional muscle damage. J Appl Physiol. 2005;99(2):564–9.PubMedGoogle Scholar
  26. 26.
    Phillips SM, Tipton KD, Aarsland A, Wolf SE, Wolfe RR. Mixed muscle protein synthesis and breakdown after resistance exercise in humans. Am J Physiol. 1997;273(1 Pt 1):E99–107.PubMedGoogle Scholar
  27. 27.
    Biolo G. Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am J Physiol Endocrinol Metab. 1995;268:E514–E20.PubMedGoogle Scholar
  28. 28.
    Macdougall JD, Gibala, MJ, Tarnapolsky, MA. The time course for elevated muscle protein synthesis following heavy resistance exercise. Can J Appl Physiol. 1995;20:480–6.PubMedGoogle Scholar
  29. 29.
    Zanchi NE, Lancha AH, Jr. Mechanical stimuli of skeletal muscle: implications on mTOR/p70s6k and protein synthesis. Eur J Appl Physiol. 2008;102(3):253–63.PubMedGoogle Scholar
  30. 30.
    Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009;296(6):C1258–70.PubMedGoogle Scholar
  31. 31.
    Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab. 2004;287(4):E591–601.PubMedGoogle Scholar
  32. 32.
    Deldicque L, Louis M, Theisen D, Nielens H, Dehoux M, Thissen JP, et al. Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med Sci Sports Exerc. 2005;37(5):731–6.PubMedGoogle Scholar
  33. 33.
    Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, et al. Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem. 2005;280(4):2737–44.PubMedGoogle Scholar
  34. 34.
    Goldspink G. Mechanical Signals, IGF-I Gene Splicing, and Muscle Adaptation. Physiology. 2005;20(4):232–8.Google Scholar
  35. 35.
    Cheema U, Brown R, Mudera V, Yang SY, McGrouther G, Goldspink G. Mechanical signals and IGF-I gene splicing in vitro in relation to development of skeletal muscle. J Cell Physiol. 2005;202(1):67–75.PubMedGoogle Scholar
  36. 36.
    Bamman MM, Petrella JK, Kim JS, Mayhew DL, Cross JM. Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans. J Appl Physiol. 2007;102(6):2232–9.PubMedGoogle Scholar
  37. 37.
    Greig CA, Hameed M, Young A, Goldspink G, Noble B. Skeletal muscle IGF-I isoform expression in healthy women after isometric exercise. Growth Horm IGF Res. 2006;16(5-6):373–6.PubMedGoogle Scholar
  38. 38.
    Psilander N, Damsgaard R, Pilegaard H. Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle. J Appl Physiol. 2003;95(3):1038–44.PubMedGoogle Scholar
  39. 39.
    Coffey VG, Reeder DW, Lancaster GI, Yeo WK, Febbraio MA, Yaspelkis BB, 3rd, et al. Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle. Med Sci Sports Exerc. 2007;39(12):2135–44.PubMedGoogle Scholar
  40. 40.
    Musaro A, McCullagh KJ, Naya FJ, Olson EN, Rosenthal N. IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature. 1999;400(6744):581–5.PubMedGoogle Scholar
  41. 41.
    Ferry RJ, Jr., Katz LE, Grimberg A, Cohen P, Weinzimer SA. Cellular actions of insulin-like growth factor binding proteins. Horm Metab Res. 1999;31(2-3):192–202.PubMedGoogle Scholar
  42. 42.
    Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16(1):3–34.PubMedGoogle Scholar
  43. 43.
    Goldberg AL, Etlinger JD, Goldspink DF, Jablecki C. Mechanism of work-induced hypertrophy of skeletal muscle. Med Sci Sports. 1975;7(3):185–98.PubMedGoogle Scholar
  44. 44.
    Marsh DR, Criswell DS, Hamilton MT, Booth FW. Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats. Am J Physiol. 1997;273(1 Pt 2):R353–8.PubMedGoogle Scholar
  45. 45.
    McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997;387(6628):83–90.PubMedGoogle Scholar
  46. 46.
    Grobet L, Martin LJ, Poncelet D, Pirottin D, Brouwers B, Riquet J, et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet. 1997;17(1):71–4.PubMedGoogle Scholar
  47. 47.
    Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci. 1998;95(25):14938–43.PubMedGoogle Scholar
  48. 48.
    Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA. Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Exp Biol Med. 2003;228(6):706–9.Google Scholar
  49. 49.
    Kostek MC, Delmonico MJ, Reichel JB, Roth SM, Douglass L, Ferrell RE, et al. Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults. J Appl Physiol. 2005;98(6):2147–54.PubMedGoogle Scholar
  50. 50.
    Hand BD, Kostek MC, Ferrell RE, Delmonico MJ, Douglass LW, Roth SM, et al. Influence of promoter region variants of insulin-like growth factor pathway genes on the strength-training response of muscle phenotypes in older adults. J Appl Physiol. 2007;103(5):1678–87.PubMedGoogle Scholar
  51. 51.
    Sayer AA, Syddall H, O’Dell SD, Chen XH, Briggs PJ, Briggs R, et al. Polymorphism of the IGF2 gene, birth weight and grip strength in adult men. Age Ageing. 2002;31(6):468–70.PubMedGoogle Scholar
  52. 52.
    Schrager MA, Roth SM, Ferrell RE, Metter EJ, Russek-Cohen E, Lynch NA, 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):2176–83.PubMedGoogle Scholar
  53. 53.
    Devaney JM, Hoffman EP, Gordish-Dressman H, Kearns A, Zambraski E, Clarkson PM. IGF-II gene region polymorphisms related to exertional muscle damage. J Appl Physiol. 2007;102(5):1815–23.PubMedGoogle Scholar
  54. 54.
    Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil. 2002;81(11 Suppl):S52–69.PubMedGoogle Scholar
  55. 55.
    Yu JG, Carlsson L, 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. 2004;121(3):219–27.PubMedGoogle Scholar
  56. 56.
    Yu JG, Furst DO, Thornell LE. The mode of myofibril remodelling in human skeletal muscle affected by DOMS induced by eccentric contractions. Histochem Cell Biol. 2003;119(5):383–93.PubMedGoogle Scholar
  57. 57.
    Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, et al. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004;350(26):2682–8.PubMedGoogle Scholar
  58. 58.
    Ferrell RE, Conte V, Lawrence EC, Roth SM, Hagberg JM, Hurley BF. Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics. 1999;62(2):203–7.PubMedGoogle Scholar
  59. 59.
    Ivey FM, Roth SM, Ferrell RE, Tracy BL, Lemmer JT, Hurlbut DE, et al. Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci. 2000;55(11):M641–8.PubMedGoogle Scholar
  60. 60.
    Walsh S, Metter EJ, Ferrucci L, Roth SM. Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans. J Appl Physiol. 2007;102(6):2142–8.PubMedGoogle Scholar
  61. 61.
    Saunders MA, Good JM, Lawrence EC, Ferrell RE, Li WH, Nachman MW. Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth. Am J Hum Genet. 2006;79(6):1089–97.PubMedGoogle Scholar
  62. 62.
    Kostek MA, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, et al. Myostatin and follistatin polymorphisms interact with muscle phenotypes and ethnicity. Med Sci Sports Exerc. 2009;41(5):1063–71.PubMedGoogle Scholar
  63. 63.
    Frost RA, Lang CH. Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass. J Appl Physiol. 2007;103(1):378–87.PubMedGoogle Scholar
  64. 64.
    Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol. 2005;288(2):R345–53.PubMedGoogle Scholar
  65. 65.
    Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999;18(49):6853–66.PubMedGoogle Scholar
  66. 66.
    Costelli P, Carbo N, Tessitore L, Bagby GJ, Lopez-Soriano FJ, Argiles JM, et al. Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model. J Clin Invest. 1993;92(6):2783–9.PubMedGoogle Scholar
  67. 67.
    Breuille D, Farge MC, Rose F, Arnal M, Attaix D, Obled C. Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis. Am J Physiol. 1993;265(4 Pt 1):E660–6.PubMedGoogle Scholar
  68. 68.
    Fernandez-Celemin L, Pasko N, Blomart V, Thissen JP. Inhibition of muscle insulin-like growth factor I expression by tumor necrosis factor-alpha. Am J Physiol Endocrinol Metab. 2002;283(6):E1279–90.PubMedGoogle Scholar
  69. 69.
    Langen RC, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB. Faseb J. 2001;15(7):1169–80.PubMedGoogle Scholar
  70. 70.
    Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF. Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. Faseb J. 2001;15(2):475–82.PubMedGoogle Scholar
  71. 71.
    Bruunsgaard H, Bjerregaard E, Schroll M, Pedersen BK. Muscle strength after resistance training is inversely correlated with baseline levels of soluble tumor necrosis factor receptors in the oldest old. J Am Geriatr Soc. 2004;52(2):237–41.PubMedGoogle Scholar
  72. 72.
    Malm C, Nyberg P, Engstrom M, Sjodin B, Lenkei R, Ekblom B, et al. Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies. J Physiol. 2000;529 Pt 1:243–62.PubMedGoogle Scholar
  73. 73.
    Dahlman JM, Wang J, Bakkar N, Guttridge DC. The RelA/p65 subunit of NF-kappaB specifically regulates cyclin D1 protein stability: implications for cell cycle withdrawal and skeletal myogenesis. J Cell Biochem. 2009;106(1):42–51.PubMedGoogle Scholar
  74. 74.
    Grounds MD, Radley HG, Gebski BL, Bogoyevitch MA, Shavlakadze T. Implications of cross-talk between tumour necrosis factor and insulin-like growth factor-1 signalling in skeletal muscle. Clin Exp Pharmacol Physiol. 2008;35(7):846–51.PubMedGoogle Scholar
  75. 75.
    Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS, Jr. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol. 1999;19(8):5785–99.PubMedGoogle Scholar
  76. 76.
    Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS, Jr. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science. 2000;289(5488):2363–6.PubMedGoogle Scholar
  77. 77.
    Millino C, Fanin M, Vettori A, Laveder P, Mostacciuolo ML, Angelini C, et al. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy. BMC Med. 2009;7:14.PubMedGoogle Scholar
  78. 78.
    Vary TC, Deiter G, Lang CH. Diminished ERK 1/2 and p38 MAPK phosphorylation in skeletal muscle during sepsis. Shock. 2004;22(6):548–54.PubMedGoogle Scholar
  79. 79.
    Buford TW, Cooke MB, Willoughby DS. Resistance exercise-induced changes of inflammatory gene expression within human skeletal muscle. Eur J Appl Physiol. 2009;107(4):463–71.PubMedGoogle Scholar
  80. 80.
    Febbraio MA, Pedersen BK. Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. Faseb J. 2002;16(11):1335–47.PubMedGoogle Scholar
  81. 81.
    Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88(4):1379–406.PubMedGoogle Scholar
  82. 82.
    Ip NY, Yancopoulos GD. Ciliary neurotrophic factor and its receptor complex. Prog Growth Factor Res. 1992;4(2):139–55.PubMedGoogle Scholar
  83. 83.
    Dennis RA, Zhu H, Kortebein PM, Bush HM, Harvey JF, Sullivan DH, et al. Muscle expression of genes associated with inflammation, growth, and remodeling is strongly correlated in older adults with resistance training outcomes. Physiol Genomics. 2009;38(2):169–75.PubMedGoogle Scholar
  84. 84.
    Nielsen AR, Mounier R, Plomgaard P, Mortensen OH, Penkowa M, Speerschneider T, et al. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J Physiol. 2007;584 (Pt 1):305–12.PubMedGoogle Scholar
  85. 85.
    Furmanczyk PS, Quinn LS. Interleukin-15 increases myosin accretion in human skeletal myogenic cultures. Cell Biol Int. 2003;27(10):845–51.PubMedGoogle Scholar
  86. 86.
    Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, Argiles JM. Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders. Exp Cell Res. 2002;280(1):55–63.PubMedGoogle Scholar
  87. 87.
    Hubal MJ, Chen TC, Thompson PD, Clarkson PM. Inflammatory gene changes associated with the repeated-bout effect. Am J Physiol Regul Integr Comp Physiol. 2008;294(5):R1628–37.PubMedGoogle Scholar
  88. 88.
    Chen YW, Hubal MJ, Hoffman EP, Thompson PD, Clarkson PM. Molecular responses of human muscle to eccentric exercise. J Appl Physiol. 2003;95(6):2485–94.PubMedGoogle Scholar
  89. 89.
    Chazaud B, Sonnet C, Lafuste P, Bassez G, Rimaniol AC, Poron F, et al. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. J Cell Biol. 2003;163(5):1133–43.PubMedGoogle Scholar
  90. 90.
    McDermott DH, Yang Q, Kathiresan S, Cupples LA, Massaro JM, Keaney JF, Jr., et al. CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation. 2005;112(8):1113–20.PubMedGoogle Scholar
  91. 91.
    Liu D, Metter EJ, Ferrucci L, Roth SM. TNF promoter polymorphisms associated with muscle phenotypes in humans. J Appl Physiol. 2008;105(3):859–67.PubMedGoogle Scholar
  92. 92.
    Ljungman P, Bellander T, Nyberg F, Lampa E, Jacquemin B, Kolz M, et al. DNA variants, plasma levels and variability of interleukin-6 in myocardial infarction survivors: results from the AIRGENE study. Thromb Res. 2009;124(1):57–64.PubMedGoogle Scholar
  93. 93.
    Roth SM, Schrager MA, Lee MR, Metter EJ, Hurley BF, Ferrell RE. 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):B1085–8.PubMedGoogle Scholar
  94. 94.
    Ruiz JR, Buxens A, Artieda M, Arteta D, Santiago C, Rodriguez-Romo G, et al. The -174 G/C polymorphism of the IL6 gene is associated with elite power performance. J Sci Med Sport. 2009.PubMedGoogle Scholar
  95. 95.
    Walston J, Arking DE, Fallin D, Li T, Beamer B, Xue Q, et al. IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women. Exp Gerontol. 2005;40(4):344–52.PubMedGoogle Scholar
  96. 96.
    Pistilli EE, Devaney JM, Gordish-Dressman H, Bradbury MK, Seip RL, Thompson PD, et al. Interleukin-15 and interleukin-15R alpha SNPs and associations with muscle, bone, and predictors of the metabolic syndrome. Cytokine. 2008;43(1):45–53.PubMedGoogle Scholar
  97. 97.
    Riechman SE, Balasekaran G, Roth SM, Ferrell RE. Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J Appl Physiol. 2004;97(6):2214–9.PubMedGoogle Scholar
  98. 98.
    Roth SM, Metter EJ, Lee MR, Hurley BF, Ferrell RE. C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women. J Appl Physiol. 2003;95(4):1425–30.PubMedGoogle Scholar
  99. 99.
    Arking DE, Fallin DM, Fried LP, Li T, Beamer BA, Xue QL, et al. Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women. J Am Geriatr Soc. 2006;54(5):823–6.PubMedGoogle Scholar
  100. 100.
    De Mars G, Windelinckx A, Beunen G, Delecluse C, Lefevre J, Thomis MA. Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women. J Appl Physiol. 2007;102(5):1824–31.PubMedGoogle Scholar
  101. 101.
    Walsh S, Kelsey BK, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, et al. CNTF 1357 G -> A polymorphism and the muscle strength response to resistance training. J Appl Physiol. 2009;107(4):1235–40.PubMedGoogle Scholar
  102. 102.
    Conwit RA, Ling S, Roth S, Stashuk D, Hurley B, Ferrell R, et al. The relationship between ciliary neurotrophic factor (CNTF) genotype and motor unit physiology: preliminary studies. BMC Physiol. 2005;5:15.PubMedGoogle Scholar
  103. 103.
    Bray MS, Hagberg JM, Perusse L, Rankinen T, Roth SM, Wolfarth B, et al. The human gene map for performance and health-related fitness phenotypes: the 2006-2007 update. Med Sci Sports Exerc. 2009;41(1):35–73.PubMedGoogle Scholar
  104. 104.
    Folland J, Leach B, Little T, Hawker K, Myerson S, Montgomery H, et al. Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload. Exp Physiol. 2000;85(5):575–9.PubMedGoogle Scholar
  105. 105.
    Pescatello LS, Kostek MA, Gordish-Dressman H, Thompson PD, Seip RL, Price TB, et al. ACE ID genotype and the muscle strength and size response to unilateral resistance training. Med Sci Sports Exerc. 2006;38(6):1074–81.PubMedGoogle Scholar
  106. 106.
    McCauley T, Mastana SS, Hossack J, Macdonald M, Folland JP. Human angiotensin-converting enzyme I/D and alpha-actinin 3 R577X genotypes and muscle functional and contractile properties. Exp Physiol. 2009;94(1):81–9.PubMedGoogle Scholar
  107. 107.
    Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int. 2002;13(3):187–94.PubMedGoogle Scholar
  108. 108.
    Windelinckx A, De Mars G, Beunen G, Aerssens J, Delecluse C, Lefevre J, et al. Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women. Osteoporos Int. 2007;18(9):1235–42.PubMedGoogle Scholar
  109. 109.
    Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A. 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):323–8.PubMedGoogle Scholar
  110. 110.
    Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53.PubMedGoogle Scholar
  111. 111.
    Liu XG, Tan LJ, Lei SF, Liu YJ, Shen H, Wang L, et al. Genome-wide association and replication studies identified TRHR as an important gene for lean body mass. Am J Hum Genet. 2009;84(3):418–23.PubMedGoogle Scholar
  112. 112.
    Tucker T, Marra M, Friedman JM. Massively parallel sequencing: the next big thing in genetic medicine. Am J Hum Genet 2009;85(2):142–54.PubMedGoogle Scholar
  113. 113.
    Schadt EE. Molecular networks as sensors and drivers of common human diseases. Nature. 2009;461(7261):218–23.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Monica J. Hubal
    • 1
  • Maria L. Urso
  • Priscilla M. Clarkson
  1. 1.Department of Integrative Systems BiologyGeorge Washington University School of Medicine, Research Center for Genetic Medicine, Children’s National Medical CenterWashingtonUSA

Personalised recommendations