Skip to main content
Top
Published in: European Journal of Applied Physiology 3/2004

01-07-2004 | Original Article

Exploration of myostatin polymorphisms and the angiotensin-converting enzyme insertion/deletion genotype in responses of human muscle to strength training

Authors: Martine A. I. Thomis, Wim Huygens, Sofie Heuninckx, Monique Chagnon, Hermine H. M. Maes, Albrecht L. Claessens, Robert Vlietinck, Claude Bouchard, Gaston P. Beunen

Published in: European Journal of Applied Physiology | Issue 3/2004

Login to get access

Abstract

This study explores the associations between polymorphisms in two candidate genes—myostatin gene (MSTN or GDF8) and angiotensin-converting enzyme (ACE) gene—with interindividual differences in human muscle mass and strength responses to strength training. The MSTN AluI A55T (exon 1), BanII K153R, TaqI E164 K and BstNI P198A (all in exon 2) markers and the ACE insertion (I)/deletion (D) polymorphism were typed in 57 males [22.4 (3.7) years] who participated in a 10-week, high-resistance training program for the elbow flexors. Maximal strength, and maximal isometric and concentric elbow flexor torques were measured at baseline and after training. Information on muscle cross-sectional area of the upper arm was obtained by computer tomography scans. Only one individual was heterozygous for the MSTN BanII K153R variant. No allelic variant was detected at the other MSTN sites in this population. For the ACE I/D polymorphism, no evidence was found for an association of the D or I allele with baseline strength, isometric and concentric torque or arm muscle cross-sectional area [analysis of covariance (ANCOVA) 0.25<P<0.97]. Responses to the strength-training program were not associated with the ACE I/D genotype (ANCOVA 0.057<P<0.70). Borderline significance was found for larger strength gains in dynamic flexion torques for I/I genotypes. This study therefore does not support the hypothesis that an increased muscle fiber hypertrophic effect of strength training is present in D-allele carriers.
Literature
go back to reference Bouchard C, Pérusse L, Leblanc C (1990) Using MZ twins in experimental research to test for the presence of a genotype-environment interaction effect. Acta Genet Med Gemellol (Roma) 39:85–89 Bouchard C, Pérusse L, Leblanc C (1990) Using MZ twins in experimental research to test for the presence of a genotype-environment interaction effect. Acta Genet Med Gemellol (Roma) 39:85–89
go back to reference Campbell H, Rudan I (2002) Interpretation of genetic association studies in complex disease. Pharmacogenomics J 2:349–360CrossRefPubMed Campbell H, Rudan I (2002) Interpretation of genetic association studies in complex disease. Pharmacogenomics J 2:349–360CrossRefPubMed
go back to reference Carlson CJ, Booth FW, Gordon SE (1999) Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading. Am J Physiol 277:R601–R606PubMed Carlson CJ, Booth FW, Gordon SE (1999) Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading. Am J Physiol 277:R601–R606PubMed
go back to reference Charlier C, Coppieters W, Farnir F, Grobet L, Leroy P, Michaux C, Mni M, Schwers A, Vanmanshoven P (1995) The mh gene causing double-muscling in cattle maps to bovine chromosome 2. Mamm Genome 6:788–792PubMed Charlier C, Coppieters W, Farnir F, Grobet L, Leroy P, Michaux C, Mni M, Schwers A, Vanmanshoven P (1995) The mh gene causing double-muscling in cattle maps to bovine chromosome 2. Mamm Genome 6:788–792PubMed
go back to reference Evans AE, Poirier O, Kee F, Lecerf L, McCrum E, Falconer T, Crane J, O’Rourke DF, Cambien F (1994) Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. Q J Med 87:211–214PubMed Evans AE, Poirier O, Kee F, Lecerf L, McCrum E, Falconer T, Crane J, O’Rourke DF, Cambien F (1994) Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. Q J Med 87:211–214PubMed
go back to reference Fatini C, Guazzelli R, Manetti P, Battaglini B, Gensini F, Vono R, Toncelli L, Zilli P, Capalbo A, Abbate R, Gensini GF, Galanti G (2000) RAS genes influence exercise-induced left ventricular hypertrophy: an elite athletes study. Med Sci Sport Exerc 32:1868–1872CrossRef Fatini C, Guazzelli R, Manetti P, Battaglini B, Gensini F, Vono R, Toncelli L, Zilli P, Capalbo A, Abbate R, Gensini GF, Galanti G (2000) RAS genes influence exercise-induced left ventricular hypertrophy: an elite athletes study. Med Sci Sport Exerc 32:1868–1872CrossRef
go back to reference Ferrell RE, Conte V, Lawrence EC, Roth SM, Hagberg JM, Hurley BF (1999) Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 62:203–207CrossRefPubMed Ferrell RE, Conte V, Lawrence EC, Roth SM, Hagberg JM, Hurley BF (1999) Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 62:203–207CrossRefPubMed
go back to reference Folland J, Leach B, Little T, Hawker K, Meyerson S, Montgomery H, Jones D (2000) Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload. Exp Physiol 85:575–579PubMed Folland J, Leach B, Little T, Hawker K, Meyerson S, Montgomery H, Jones D (2000) Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload. Exp Physiol 85:575–579PubMed
go back to reference Gonzalez-Cadavid N, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S (1998) Organization of the human myostatin gene and expression in healthy men and HIV infected men with muscle waisting. Proc Natl Acad Sci U S A 95:14938–14943CrossRefPubMed Gonzalez-Cadavid N, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S (1998) Organization of the human myostatin gene and expression in healthy men and HIV infected men with muscle waisting. Proc Natl Acad Sci U S A 95:14938–14943CrossRefPubMed
go back to reference Grobet L, Poncelet D, Royo LJ, Brouwers B, Pirottin D, Michaux C, Menissier F, Zanotti M, Dunner S, Georges M (1998) Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle. Mamm Genome 9:210–213CrossRefPubMed Grobet L, Poncelet D, Royo LJ, Brouwers B, Pirottin D, Michaux C, Menissier F, Zanotti M, Dunner S, Georges M (1998) Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle. Mamm Genome 9:210–213CrossRefPubMed
go back to reference Hakkinen K, Newton RU, Gordon SE, McCormick M, Volek JS, Nindl BS, Gotshalk LA, Campbell WW, Evans W, Hakkinen A, Humphries BJ, Kraemer WJ (1998) Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and old men. J Gerontol 53A:B415–B423 Hakkinen K, Newton RU, Gordon SE, McCormick M, Volek JS, Nindl BS, Gotshalk LA, Campbell WW, Evans W, Hakkinen A, Humphries BJ, Kraemer WJ (1998) Changes in muscle morphology, electromyographic activity, and force production characteristics during progressive strength training in young and old men. J Gerontol 53A:B415–B423
go back to reference 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–H2663PubMed 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–H2663PubMed
go back to reference Ivey FM, Roth SM, Ferrell RE, Tracy BL, Lemmer JT, Hurlbut DE, Martel GF, Siegel EL, Fozard JL, Metter EJ, Fleg JL, Hurley BF (2000) Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci 55:M641–M648PubMed Ivey FM, Roth SM, Ferrell RE, Tracy BL, Lemmer JT, Hurlbut DE, Martel GF, Siegel EL, Fozard JL, Metter EJ, Fleg JL, Hurley BF (2000) Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci 55:M641–M648PubMed
go back to reference Jones A, Montgomery HE, Woods DR (2002) Human performance: a role for the ACE genotype? Exerc Sport Sci Rev 30:184–190CrossRefPubMed Jones A, Montgomery HE, Woods DR (2002) Human performance: a role for the ACE genotype? Exerc Sport Sci Rev 30:184–190CrossRefPubMed
go back to reference Jonsson JR, Smid SD, Frewin DB, Head RJ (1993) Angiotensin II-mediated facilitation of sympathetic neurotransmission in the spontaneously hypertensive rat is not associated with neuronal uptake of the peptide. J Cardiovasc Pharmacol 22:750–753PubMed Jonsson JR, Smid SD, Frewin DB, Head RJ (1993) Angiotensin II-mediated facilitation of sympathetic neurotransmission in the spontaneously hypertensive rat is not associated with neuronal uptake of the peptide. J Cardiovasc Pharmacol 22:750–753PubMed
go back to reference Kambadur R, Sharma M, Smith TPL, Bass JJ (1997) Mutations in myostatin (GDF8) in double-muscled Belgian Blue en Piedmontese cattle. Genome Res 7:910–916PubMed Kambadur R, Sharma M, Smith TPL, Bass JJ (1997) Mutations in myostatin (GDF8) in double-muscled Belgian Blue en Piedmontese cattle. Genome Res 7:910–916PubMed
go back to reference Kraemer WJ, Fleck SJ, Evans WJ (1996) Strength and power training: physiological mechanisms of adaptation. Exerc Sport Sci Rev 24:363–397PubMed Kraemer WJ, Fleck SJ, Evans WJ (1996) Strength and power training: physiological mechanisms of adaptation. Exerc Sport Sci Rev 24:363–397PubMed
go back to reference McPherron AC, Lee S-J (1997b) Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A 94:12457–12461CrossRefPubMed McPherron AC, Lee S-J (1997b) Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A 94:12457–12461CrossRefPubMed
go back to reference McPherron AC, Lawler AM, Lee S-J (1997a) Regulation of skeletal muscle mass in mice by a new TGF-b superfamily member. Nature 387:83–90PubMed McPherron AC, Lawler AM, Lee S-J (1997a) Regulation of skeletal muscle mass in mice by a new TGF-b superfamily member. Nature 387:83–90PubMed
go back to reference Messerli FH, Nowaczynski W, Honda M, Genest J, Boucher R, Kuchel O, Rojo-Ortega JM (1977) Effects of angiotensin II on steroid metabolism and hepatic blood flow in man. Circ Res 40:204–207PubMed Messerli FH, Nowaczynski W, Honda M, Genest J, Boucher R, Kuchel O, Rojo-Ortega JM (1977) Effects of angiotensin II on steroid metabolism and hepatic blood flow in man. Circ Res 40:204–207PubMed
go back to reference Montgomery H, Clarkson P, Dollery C, Prasad K, Losi M-A, Hemingway H, Statters D, Jubb M, Girvain M, Varnava A, World M, Deanfield J, Talmud P, McEwan JR, McKenna WJ, Humphries S (1997) Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training. Circulation 96:741–747PubMed Montgomery H, Clarkson P, Dollery C, Prasad K, Losi M-A, Hemingway H, Statters D, Jubb M, Girvain M, Varnava A, World M, Deanfield J, Talmud P, McEwan JR, McKenna WJ, Humphries S (1997) Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training. Circulation 96:741–747PubMed
go back to reference Montgomery HE, Clarkson P, Barnard M, Bell J, Brynes A, Dollery C, Hajnal J, Hemingway H, Mercer D, Jarman P, Marschall R, Prasad K, Rayson K, Saeed N, Talmud P, Thomas L, Jubb M, World M, Humphries S (1999) Angiotensin-converting-enzyme gene insertion/deletion polymorphism and the response to physical training. Lancet 353:541–545PubMed Montgomery HE, Clarkson P, Barnard M, Bell J, Brynes A, Dollery C, Hajnal J, Hemingway H, Mercer D, Jarman P, Marschall R, Prasad K, Rayson K, Saeed N, Talmud P, Thomas L, Jubb M, World M, Humphries S (1999) Angiotensin-converting-enzyme gene insertion/deletion polymorphism and the response to physical training. Lancet 353:541–545PubMed
go back to reference Nazarov IB, Woods DR, Montgomery HE, Shneider OV, Kazakov VI, Tomilin NV, Rogozkin VA (2001) The angiotensin converting enzyme I/D polymorphism in Russian athletes. Eur J Hum Genet 9:797–801CrossRefPubMed Nazarov IB, Woods DR, Montgomery HE, Shneider OV, Kazakov VI, Tomilin NV, Rogozkin VA (2001) The angiotensin converting enzyme I/D polymorphism in Russian athletes. Eur J Hum Genet 9:797–801CrossRefPubMed
go back to reference Rankinen T, Pérusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C (2002) The human gene map for performance and health-related fitness phenotypes: the 2001 update. Med Sci Sports Exerc 34:1219–1233CrossRefPubMed Rankinen T, Pérusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C (2002) The human gene map for performance and health-related fitness phenotypes: the 2001 update. Med Sci Sports Exerc 34:1219–1233CrossRefPubMed
go back to reference Reardon KA, Davis J, Kapsa RMI, Choong P, Byrne E (2001) Myostatin, insulin-like growth factor-1, and leukemia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy. Muscle Nerve 24:893–899CrossRefPubMed Reardon KA, Davis J, Kapsa RMI, Choong P, Byrne E (2001) Myostatin, insulin-like growth factor-1, and leukemia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy. Muscle Nerve 24:893–899CrossRefPubMed
go back to reference Reneland R, Lithell H (2001) Angiotensin-converting enzyme in human skeletal muscle: a simple in vitro assay of activity in needle biopsy specimens. Scand J Clin Lab Invest 54:105–111 Reneland R, Lithell H (2001) Angiotensin-converting enzyme in human skeletal muscle: a simple in vitro assay of activity in needle biopsy specimens. Scand J Clin Lab Invest 54:105–111
go back to reference Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley B, Rogers MA (2003) Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Exp Biol Med 228:706–709 Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley B, Rogers MA (2003) Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Exp Biol Med 228:706–709
go back to reference Sadoshima J, Xu Y, Slayter HS, Izumo S (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984PubMed Sadoshima J, Xu Y, Slayter HS, Izumo S (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984PubMed
go back to reference Sakuma K, Watanabe K, Sano M, Uramoto I, Totsuka T (2000) Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles. Biochim Biophys Acta 1497:77–88CrossRefPubMed Sakuma K, Watanabe K, Sano M, Uramoto I, Totsuka T (2000) Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles. Biochim Biophys Acta 1497:77–88CrossRefPubMed
go back to reference Sale DG (1992) Neural adaptations to strength training. In: Komi P (ed) Strength and power in sports: The encyclopaedia of sports medicine. Blackwell, Oxford, pp 249–265 Sale DG (1992) Neural adaptations to strength training. In: Komi P (ed) Strength and power in sports: The encyclopaedia of sports medicine. Blackwell, Oxford, pp 249–265
go back to reference Schaufelberger M, Drexler H, Csheiffer E, Swedberg K (1998) Angiotensin-converting enzyme gene expression in skeletal muscle in patients with chronic heart failure. J Card Fail 4:185–191PubMed Schaufelberger M, Drexler H, Csheiffer E, Swedberg K (1998) Angiotensin-converting enzyme gene expression in skeletal muscle in patients with chronic heart failure. J Card Fail 4:185–191PubMed
go back to reference Seibert MJ, Xue QL, Fried, Walston JD (2001) Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women’s Health and Aging Study II cohort. J Am Geriatr Soc 49:1093–1096CrossRefPubMed Seibert MJ, Xue QL, Fried, Walston JD (2001) Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women’s Health and Aging Study II cohort. J Am Geriatr Soc 49:1093–1096CrossRefPubMed
go back to reference Sharma M, Langley B, Bass J, Kambadur R (2001) Myostatin in muscle growth and repair. Exerc Sport Sci Rev 29:155–158CrossRefPubMed Sharma M, Langley B, Bass J, Kambadur R (2001) Myostatin in muscle growth and repair. Exerc Sport Sci Rev 29:155–158CrossRefPubMed
go back to reference Sonna LA, Sharp MA, Knapik JJ, Cullivan M, Angel KC, Patton JF, Lilly CM (2001) Angiotensin-converting enzyme genotype and physical performance during US Army basic training J Appl Physiol 91:1355–1363 Sonna LA, Sharp MA, Knapik JJ, Cullivan M, Angel KC, Patton JF, Lilly CM (2001) Angiotensin-converting enzyme genotype and physical performance during US Army basic training J Appl Physiol 91:1355–1363
go back to reference Thomis M, Claessens AL, Vlietinck R, Marchal G, Beunen G (1997) Accuracy of anthropometric estimation of muscle cross-sectional area of the arm in males. Am J Hum Biol 9:73–86CrossRef Thomis M, Claessens AL, Vlietinck R, Marchal G, Beunen G (1997) Accuracy of anthropometric estimation of muscle cross-sectional area of the arm in males. Am J Hum Biol 9:73–86CrossRef
go back to reference Thomis MA, Beunen GP, Maes HH, Blimkie CJ, Van Leemputte M, Claessens AL, Marchal G, Willems E, Vlietinck R (1998) Strength training: importance of genetic factors. Med Sci Sports Exerc 30:724–731CrossRefPubMed Thomis MA, Beunen GP, Maes HH, Blimkie CJ, Van Leemputte M, Claessens AL, Marchal G, Willems E, Vlietinck R (1998) Strength training: importance of genetic factors. Med Sci Sports Exerc 30:724–731CrossRefPubMed
go back to reference Thomis MA, Huygens W, Peeters M, Loos R, Van Langendonck L, Lefevre J, Claessens AL, Chagnon M, Vlietinck R, Bouchard C (2001) The ACE I/D polymorphism and body dimensions in strength athletes versus controls. Med Sci Sports Exerc 33:S323 Thomis MA, Huygens W, Peeters M, Loos R, Van Langendonck L, Lefevre J, Claessens AL, Chagnon M, Vlietinck R, Bouchard C (2001) The ACE I/D polymorphism and body dimensions in strength athletes versus controls. Med Sci Sports Exerc 33:S323
go back to reference Van Leemputte M, Willems E (1987) EMG quantification and its application to the analysis of human movements. Med Sci Sports 25:177–194 Van Leemputte M, Willems E (1987) EMG quantification and its application to the analysis of human movements. Med Sci Sports 25:177–194
go back to reference Wali FA (1986) Effect of angiotensin II on mechanical and electrical responses of frog, chick and rat skeletal muscle. Arch Int Pharmacodyn Ther 282:314–327PubMed Wali FA (1986) Effect of angiotensin II on mechanical and electrical responses of frog, chick and rat skeletal muscle. Arch Int Pharmacodyn Ther 282:314–327PubMed
go back to reference Woods D, Onambele G, Woledge R, Skelton D, Bruce S, Humphries SE, Montgomery H (2001) Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density. J Clin Endocrinol Metab 86:2200–2204CrossRefPubMed Woods D, Onambele G, Woledge R, Skelton D, Bruce S, Humphries SE, Montgomery H (2001) Angiotensin-I converting enzyme genotype-dependent benefit from hormone replacement therapy in isometric muscle strength and bone mineral density. J Clin Endocrinol Metab 86:2200–2204CrossRefPubMed
go back to reference Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF (2002) Serum myostatin-immunoreactive protein is increased in 60–92 year old women and men with muscle wasting. J Nutr Health Aging 6:343–348PubMed Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF (2002) Serum myostatin-immunoreactive protein is increased in 60–92 year old women and men with muscle wasting. J Nutr Health Aging 6:343–348PubMed
Metadata
Title
Exploration of myostatin polymorphisms and the angiotensin-converting enzyme insertion/deletion genotype in responses of human muscle to strength training
Authors
Martine A. I. Thomis
Wim Huygens
Sofie Heuninckx
Monique Chagnon
Hermine H. M. Maes
Albrecht L. Claessens
Robert Vlietinck
Claude Bouchard
Gaston P. Beunen
Publication date
01-07-2004
Publisher
Springer-Verlag
Published in
European Journal of Applied Physiology / Issue 3/2004
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI
https://doi.org/10.1007/s00421-004-1093-6

Other articles of this Issue 3/2004

European Journal of Applied Physiology 3/2004 Go to the issue