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ACE I/D and ACTN3 R/X polymorphisms and muscle function and muscularity of older Caucasian men

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Abstract

The progressive decline in strength and power with ageing leads to compromised mobility and an increased risk of falls. Angiotensin converting enzyme (ACE) I/D and alpha actinin 3 (ACTN3) R/X polymorphisms have been suggested to influence variations in skeletal muscle function and body composition. This study investigated the associations between these polymorphisms and knee extensor muscle function and muscularity in older Caucasian men. Strength was measured isometrically and isokinetically (at 30 and 240° s−1), and the time course of the evoked twitch response recorded. A dual-energy X-ray absorptiometry scan measured thigh and whole body non-skeletal lean mass. ACE I/D and ACTN3 R/X polymorphisms were determined by polymerase chain reaction, and serum ACE activity using spectrophotometry. Whole body and thigh non-skeletal lean mass were independent of ACE and ACTN3 genotypes. Absolute and relative high velocity strength, and the time course of an evoked twitch were not associated with ACE or ACTN3 genotype. Serum ACE activity was negatively correlated with relative high velocity torque (R = −0.23, P = 0.03), and exhibited a positive trend with knee extensor isometric strength (R = 0.19, P = 0.07). ACE I/D and ACTN3 R/X polymorphisms were not associated with muscle function or muscularity phenotypes in older Caucasian men, although serum ACE activity appeared to have a small effect on muscle function.

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References

  • Akhmetov II, Astratenkova IV, Druzhevskaia AM, Komkova AI, Liubaeva EV, Tarakin PP, Shenkman BS, Rogozkin VA (2006) The association of gene polymorphisms with the muscle fibre type composition. Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova/Rossiĭskaia akademiia nauk 92:883–888

    CAS  PubMed  Google Scholar 

  • Carmelli D, Kelly-Hayes M, Wolf PA, Swan GE, Jack LM, Reed T, Guralnik JM (2000) The contribution of genetic influences to measures of lower extremity function in older male twins. J Gerontol Ser A Biol Sci 55(1):49–53

    Google Scholar 

  • Chan S, Seto JT, MacArthur DG, Yang N, North KM, Head SI (2008) A gene for speed: contractile properties of isolated whole EDL muscle from an alpha-actinin-3 knockout mouse. Am J Physiol Cell Physiol 295(4):C897–C904

    Article  CAS  PubMed  Google Scholar 

  • Charbonneau DE, Hanson ED, Ludlow AT, Delmonico MJ, Hurley BF, Roth SM (2008) ACE genotype and the muscle hypertrophic and strength responses to strength training. Med Sci Sports Exerc 40(4):677–683

    Article  CAS  PubMed  Google Scholar 

  • Clarkson PM, Devaney JM, Gordish-Dressman H, Thompson PD, Hubal MJ, Urso M, Price TB, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Hoffman EP (2005) ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol 99:154–163

    Article  CAS  PubMed  Google Scholar 

  • Delmonico MJ, Zmuda JM, Taylor BC, Cauley JA, Harris TB, Manini TM, Schwartz A, Li R, Roth SM, Hurley BF, Bauer DC, Ferrell RE, Newman AB, Health ABC and MrOS Research Groups (2008) Association of the ACTN3 genotype and physical functioning with age in older adults. J Gerontol Ser A Biol Sci Med Sci 63(11):1227–1234

    Google Scholar 

  • Druzhevskaya AM, Ahmetov II, Astratenkova IV, Rogozkin VA (2008) Association of the ACTN3 R577X polymorphism with power athlete status in Russians. Eur J Appl Physiol 103(6):631–634

    Article  CAS  PubMed  Google Scholar 

  • Edwards RHT, Young A, Hosking GP, Jones DA (1977) Human skeletal muscle function: description of tests and normal values. Clin Sci Mol Med 52:283–290

    CAS  PubMed  Google Scholar 

  • Folland JP, Williams AG (2007) The adaptations to strength training. Morphological and neurological contributions to increased strength. Sports Med 37(2):145–168

    Article  PubMed  Google Scholar 

  • Folland JP, Leach B, Little T, Hawker K, Myerson S, Montgomery H, Jones DA (2000) Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload. Exp Physiol 85:575–579

    Article  CAS  PubMed  Google Scholar 

  • Frederiksen H, Bathum L, Worm C, Chistensen K (2003) ACE genotype and physical training effects: a randomized study among elderly Danes. Aging Clin Exp Res 15:284–291

    CAS  PubMed  Google Scholar 

  • Gordon SE, Davis BS, Carlson CJ, Booth FW (2001) ANG II is required for optimal overload-induced skeletal muscle hypertrophy. Am J Physiol Endocrinol Metab 280:150–159

    Google Scholar 

  • Gür H, Gransberg L, vanDyke D, Knutsson E, Larsson L (2003) Relationship between in vivo muscle force at different speeds of isokinetic movements and myosin isoform expression in men and women. Eur J Appl Physiol 88:487–496

    Article  PubMed  Google Scholar 

  • Hopkinson NS, Nickol AH, Payne J, Hawe E, Man W, Moxham J, Montgomery H, Polkey MI (2004) ACE gene and strength in COPD. Am J Respir Crit Care Med 170:395–399

    Article  PubMed  Google Scholar 

  • Ishigai Y, Mori T, Ikeda T, Fukuzawa A, Shibano T (1997) Role of bradykinin-NO pathway in prevention of cardiac hypertrophy by ACE inhibitor in rat cardiomyocytes. Am J Physiol 273:H2659–H2663

    CAS  PubMed  Google Scholar 

  • Izquierdo M, Ibanez J, Gorastiag E, Garrues M, Zuniga A, Anton A, Larrion JL, Hakkinen K (1999) Maximal strength and power characteristics in isometric and dynamic actions of the upper and lower extremities in middle-aged and older men. Acta Physiol Scand 167(1):57–68

    Article  CAS  PubMed  Google Scholar 

  • Lexell J (1995) Human aging, muscle mass, and fiber type composition. J Gerontol Ser A Biol Sci Med Sci 50, spec no. 11–16

  • MacArthur DG, Seto JT, Chan S, Quinlan KG, Raftery JM, Turner N, Nicholson MD, Kee AJ, Hardeman EC, Gunning PW, Cooney GJ, Head SI, Yang N, North KN (2008) An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance. Hum Mol Genet 15:1076–1086

    Article  Google Scholar 

  • Mc Cauley TM, Mastana SS, Hossack J, MacDonald M, Folland JP (2009) Human angiotensin-converting enzyme I/D and α-actinin3 R577X genotypes and muscle functional and contractile properties. Exp Physiol 94(1):81–89

    Article  CAS  Google Scholar 

  • Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K (2001) Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. Hum Mol Genet 10:1335–1346

    Article  CAS  PubMed  Google Scholar 

  • Myerson SG, Hemingway H, Budget R, Martin J, Humphries S, Montogmery H (1999) Human angiotensin I-converting enzyme gene and endurance performance. J Appl Physiol 87(4):1313–1316

    CAS  PubMed  Google Scholar 

  • Niemi A, Majamaa K (2005) Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet 13:965–969

    Article  CAS  PubMed  Google Scholar 

  • Norman B, Esbjörnsson M, Rundqvist H, Osterlund T, von Walden F, Tesch PA (2009) Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol 106(3):959–965

    Article  CAS  PubMed  Google Scholar 

  • Parker DF, Round JM, Sacco P, Jones DA (1990) A cross sectional survey of upper and lower limb strength in boys and girls during childhood and adolescence. Ann Hum Biol 17:199–221

    Article  CAS  PubMed  Google Scholar 

  • Pescatello LS, Kostek MA, Gordish-Dressman H, Thompson PD, Seip RL, Price TB, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, Zoeller RF, Devaney JM, Hoffman EP (2006) ACE ID genotype and muscle strength and size response to unilateral resistance training. Med Sci Sports Exerc 38:1074–1081

    Article  CAS  PubMed  Google Scholar 

  • Roos MR, Rice CL, Connelly DM, Vandervoort AA (1999) Quadriceps muscle strength, contractile properties, and motor unit firing rates in young and old men. Muscle Nerve 22:1094–1103

    Article  CAS  PubMed  Google Scholar 

  • Roth SM, Walsh S, Liu D, Metter EJ, Ferrucci L, Hurley BF (2008) The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Eur J Hum Genet 16(3):391–394

    Article  CAS  PubMed  Google Scholar 

  • Skelton DA, Greig CA, Davies JM, Young A (1994) Strength, power and related functional ability of healthy people aged 65–89 years. Age Ageing 23(5):371–377

    Article  CAS  PubMed  Google Scholar 

  • Tiainen K, Pajala S, Spila S, Kaprio J, Koskenvuo M, Alen M, Heikkinen E, Tolvanen A, Rantanen T (2007) Genetic effects in common on maximal walking speed and muscle performance in older women. Scand J Med Sci Sports 17:274–280

    CAS  PubMed  Google Scholar 

  • Vincent B, DeBock K, Ramaekers M, Van Den Eede E, Van Leemputte M, Hespel P, Thomis M (2007) The ACTN3 (R577X) genotype is associated with fibre type distribution. Physiol Genom 32:58–63

    Article  CAS  Google Scholar 

  • Walsh S, Liu D, Metter EJ, Ferrucci L, Roth SM (2008) ACTN3 genotype is associated with muscle phenotypes in women across the adult age span. J Appl Physiol 105(5):1486–1491

    Article  PubMed  Google Scholar 

  • Westerkamp CM, Gordon SE (2005) Angiotensin-converting enzyme inhibition attenuates myonuclear addition in overloaded slow-twitch skeletal muscle. Am J Physiol Regul Integr Comp Physiol 289(4):R1223–R1231

    CAS  PubMed  Google Scholar 

  • Williams AG, Folland JP (2008) Similarity of polygenic profiles limits the potential for elite human physical performance. J Physiol 586(1):113–1231

    Article  CAS  PubMed  Google Scholar 

  • Williams AG, Day SH, Folland JP, Gohlke P, Dhamrait S, Montgomery HE (2005) Circulating angiotensin converting enzyme activity is correlated with muscle strength. Med Sci Sports Exerc 37:944–948

    CAS  PubMed  Google Scholar 

  • Woods D, Hickman M, Jamshidi Y, Brull D, Vassiliou V, Jones A, Humphries S, Montgomery H (2001a) Elite swimmers and the D allele of the ACE I/D polymorphism. Hum Genet 108(3):230–232

    Article  CAS  PubMed  Google Scholar 

  • Woods D, Onambele G, Woledge R, Skelton D, Bruce S, Humphries SE, Montgomery H (2001b) Angiotensin I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density. J Clin Endocrinol Metab 86:2200–2204

    Article  CAS  PubMed  Google Scholar 

  • Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K (2003) ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 73:627–631

    Article  CAS  PubMed  Google Scholar 

  • Zhang B, Tanaka H, Shono N, Miura S, Kiyonaga A, Shindo M, Saku K (2003) The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibres in human skeletal muscle. Clin Genet 62(2):139–144

    Article  Google Scholar 

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Correspondence to Tracey McCauley.

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Communicated by Susan Ward.

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McCauley, T., Mastana, S.S. & Folland, J.P. ACE I/D and ACTN3 R/X polymorphisms and muscle function and muscularity of older Caucasian men. Eur J Appl Physiol 109, 269–277 (2010). https://doi.org/10.1007/s00421-009-1340-y

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