ACE DD Genotype is Unfavorable to Korean Short-Term Muscle Power Athletes

Abstract

The purpose of this study was to test the hypothesis that the ACE DD genotype is unfavorably associated with the ultimate power-oriented performance. To test the hypothesis we recruited a total of 848 subjects including 55 international level power-oriented athletes (High-performance), 100 national level power-oriented athletes (Mid-performance) and 693 healthy controls (Control) in Korea. Then the distributions of ACE polymorphism throughout these groups were analyzed. As a result, there was a gradual decrease of frequencies of the DD genotype with advancing levels of performance (Control vs. Mid-performance vs. High-performance=17.2% vs. 10.0% vs. 5.5%, p=0.002). Also, the frequencies of D allele decreased gradually with advancing levels of performance (Control vs. Mid-performance vs. High-performance=42.6% vs. 35.0% vs. 30.9%, p<0.01). Therefore, power-oriented athletes at the top level had a markedly diminished frequency of the DD genotype and the D allele. This finding gave 3.83 times lower probability of success in power-oriented sports for individuals with the DD genotype than those with the II+ID genotype. In conclusion, these results indicate that Korean power-oriented athletes with a lower frequency of the DD genotype had a lower probability of success in power-oriented sports.

Key words

angiotensin-converting enzyme - population genetics - physical performance - anaerbic muscle power

References

• 1 Alvarez R, Terrados N, Ortolano R, Iglesias-Cubero G, Reguero JR, Batalla A, Cortina A, Fernandez-Garcia B, Rodriguez C, Braga A, Cortina A, Feranadez-Garcia B, Rodriguez C, Braga S, Alvarez V, Coto E. Genetic variation in the renin-angiotensin system and athletic performance.  Eur J Appl Physiol. 2000;  82 117-120
• 2 Amir O, Amir R, Yamin C, Attias E, Eynon N, Sagiv M, Sagiv M, Meckel Y. The ACE deletion allele is associated with Israeli elite endurance athletes.  Exp Physiol. 2007;  92 881-886
• 3 Bedair HS, Karthikeyan T, Quintero A, Li Y, Huard J. Angiotensin II receptor blockade administered after injury impoves muscle regeneration and decreases fibrosis in normal skeletal muscle.  Am J Sports Med. 2008;  36 1548-1554
• 4 Bouchard C, Malina RM, Perusse L. (eds). Genetics of fitness and physical performance. Champaign:Human Kinetics 1997
• 5 Brawn J. (ed). Sports Talent. Champaign:Human Kinetics 2001
• 6 Brink M, Price SR, Chrast J, Bailey JL, Anwar A, Mitch WE, Delafontaine P. Angiotensin II induces skeletal muscle wasting through enhanced protein degradation and down-regulates autocrine insulin-like growth factor-I.  Endocrinology. 2001;  142 1489-1496
• 7 Brink M, Wellen J, Delafontaine R. Angiotensin II cause weight loss and decreases ciculating insulin-like growth factor I in rats through a presser-independent mechanism.  J Clin Invest. 1996;  97 2509-2516
• 8 Cambien F, Alhenc-Gelas F, Herbeth B, Andre L, Rakotovao R, Gonzales M, Allegrini J, Bloch C. Familial resemblance of plasma angiotensin-converting enzyme level: The Nancy Study.  Am J Hum Genet. 1988;  43 744-780
• 9 Chamberlin JS. ACE inhibitor bulks up muscle.  Nat Med. 2007;  13 125-126
• 10 Cohn RD, van Erp C, Habashi JP, Soleimani AA, Klein EC, Lisi MT, Gamradi M, Rhys C, Holm TM, Loeys BL, Ramirez F, Judge DP, Ward CW, Dietz HC. Angiotensin II type 1 receptor blockade attenuates TGF-β-induced failure of muscle regeneration in multiple myopathic states.  Nat Med. 2007;  13 204-210
• 11 Collins M, Xenophontos SL, Cariolou MA, Mokene GG, Hudson DE, Anastasiades L, Noakes TD. The ACE gene and endurance performance during the South African ironman triathlons.  Med Sci Sports Exerc. 2004;  36 1314-1320
• 12 Costerousse O, Allegrini J, Lopez M, Alhenc-gelas F. Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes.  Biochem J. 1993;  290 33-40
• 13 Davies K, Baker J. Genes, environment and sport performance: Why the nature-nurture dualism is no longer relevant.  Sports Med. 2007;  37 961-980
• 14 DiBari M, van de Poll-Franse L, Onder G, Kritchevsky S, Newman A, Harris TB, Williamson JD, Marchionni N, Pahor M. Antihypertensive medications and differences in muscle mass in older persons: the Health, Aging and Body Composition Study.  J Am Geriatr Soc. 2004;  52 961-966
• 15 Dzau VJ, Gibbons GH, Pratt RE. Molecular mechanisms of vascular renin-angiotensin system in myointimal hyperplasia.  Hypertension. 1991;  18 II100-II105
• 16 Folland J, Leach B, Little T, Hawker K, Myerson S, Montgomery H, Jones D. Angiotensin-converting enzyme genotype effect affects the response of human skeletal muscle to functional overload.  Exp Physiol. 2000;  85 575-579
• 17 Gayagay G, Yu B, Hambly B, Boston T, Hahn A, Celermajer DS. Elite endurance athletes and the ACE I allele – the role of genes in athletic performance.  Hum Genet. 1998;  103 48-50
• 18 Jeong K-H, Lee T-W, Ihm C-G, Lee S-H, Moon J-Y. Polymorphism in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean population patients on maintenance hemodialysis.  Ex Mol Med. 2008;  40 161-166
• 19 Hagberg JM, McCole SD, Brown MD, Ferrell RE, Wilund KR, Humerty A, Douglass LW, Moore GE. ACE insertion/deletion polymorphism in postmenopausal women.  J Appl Physiol. 2002;  92 1083-1088
• 20 Henriksen EJ, Jacob S. Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition.  J Cell Physiol. 2003;  196 171-179
• 21 Hubert C, Hout AM, Corvol P, Soubrier F. Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene.  J Biol Chem. 1991;  15 15377-15388
• 22 Jin H-H, Kwak K-D, Hammer YN, Shinka T, Lee J-W, Jin F, Jia X, Tyler-Smith C, Kim W. Y-chromosome DNA haplogroups and their implications for the dual origins of the Koreans.  Hum Genet. 2003;  114 27-35
• 23 Jones A, Woods DR. Skeletal muscle RAS and exercise performance.  Int J Biochem Cell Biol. 2003;  855-866
• 24 Karjalainen J, Kujala UM, Stolt A, Mantysaari M, Viitasalo M, Kainulainen, Kontula. Angiotensinogen Gene M235 T polymorphism predict left ventricular hypertrophy in undurance athletes.  J Am Coll Cardiol. 1999;  34 494-499
• 25 Macintoch BR, Gardiner PF, MacComas AJ. (eds). Skeletal muscle: Form and function. Champaign: Human Kinetics 2005
• 26 Montgomery H, Clarkson P, Barnard M, Bell J, Brynes A, Dollery C, Hajnal J, Hemingway H, Mercer D, Jarman P, Marshall R, Prasad K, Rayson M, Saeed N, Talmud P, Thomas L, Jubb M, World M, Humphries S. Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.  Lancet. 1999;  353 541-545
• 27 Montgomery HE, Marshall HH, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Barnard M, Bell JD. Human gene for physical performance.  Nature. 1998;  393 221-22 222 
• 28 Myerson S, Hemingway H, Budget R, Martin J, Humphries S, Montgomery H. Human angiotensin I-converting enzyme gene and endurance performance.  J Appl Physiol. 1999;  87 1313-1316
• 29 Nazarov IB, Woods, DR, Monthomery HE, Shneider OV, Kazakov VI, Tomilin NT, Rogozkin VA. The angiotensin converting enzyme I/D polymorphism in Russian athletes.  Eur J Hum Genet. 2001;  9 797-801
• 30 Onder G, Pennix BW, Balkrishnan R, Fried LP, Chaves PH, Williamson J, Carter C, Bari, MD, Guralnik JM, Pahor M. Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study.  Lancet. 2002;  359 926-930
• 31 Park H-Y, Kwon H-M, Kim D, Jang Y, Shim WH, Cho S-Y, Kim H-S. The angiotensin converting enzyme genetic polymorphism in acute coronary syndrome – ACE polymorphism as a risk factor of acute coronary syndrome -.  J Kor Med Sci. 1997;  12 391-397
• 32 Payne JR, Dhamrait SS, Gohlke P, Cooper J, Scott RA, Pitsiladis YP, Humphries SE, Rayner B, Montgomery HE. The impact of ACE genotype on serum ACE activity in a Black South African male population.  Ann Hum Genet. 2007;  71 1-7
• 33 Powers SK, Howley ET. (eds). Exercise physiology: Theory and Application to Fitness and Performance. New York: McGraw-Hill 2001
• 34 Praagh EV, Dore E. Short-term muscle power during growth and maturation.  Sports Med. 2002;  32 701-728
• 35 Rankinnen T, Wolfarth B, Simoneau J, Maier-Lenz D, Rauramaa R, Rivera MA, Boulay MR, Chagnon YC, Perusse L, Keul J, Bouchard C. No association between the angiotensin-converting enzyme ID polymorphism and elite enduarance athlete status.  J Appl Physiol. 2000;  88 1571-1575
• 36 Rankinen T, Perusse L, Gagnon J, Chagnon YC, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study.  J Appl Physiol. 2000;  88 1029-1035
• 37 Rakugi H, Kim D-K, Krieger JE, Wang DS, Dzau VJ, Pratt E. Induction of angiotensin converting in the neointima after vascular injury.  J Clin Invest. 1994;  93 339-346
• 38 Reneland R, Lithell H. Angiotensin-converting enzyme in human skeletal muscle.  A simple in vitro assay of activity in needle biopsy specimens. Sand J Clin Lab Invest. 1994;  54 105-111
• 39 Rigat B, Huber C, Alhenc-Gelas F, Cambien F, Covol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.  J Clin Invest. 1990;  86 1343-1346
• 40 Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1).  Nucleic Acids Res. 1992;  20 1433
• 41 Russell ST, Eley H, Tisdale MJ. Mechanism of attenuation of angiotensin-II-induced protein degradation by insulin-like growth factor-I (IGF-I).  Cell Signal. 2007;  19 1583-1595
• 42 Russell ST, Eley H, Tisdale MJ. Role of reactive oxygen species in protein degradation in murin myotubes induced by proteolysis-inducing factor and angiotensin II.  Cell Signal.. 2007;  19 1797-1806
• 43 Russell ST, Sanders PM, Tisdale MJ. Angiotensin II directly inhibits protein synthesis in murine myotubes.  Cancer Lett. 2006;  231 290-294
• 44 Sanders RM, Russell ST, Tisdale MJ. Angiotensin II directly induces muscle protein catabolism through the ubiquitin-proeasome proteolytic pathway and may play a role in cancer cachexia.  Br J Cancer. 2005;  22 425-434
• 45 Saris JJ, van Dijk MA, Kroon I, Schalekamp MA, Danser AH. Functional importance of angiotensin-converting enzyme-dependent in situ angiotensin II generation in the human forearm.  Hypertension. 2000;  35 764-768
• 46 Sayed-Tabatabaei F, Oostra B, Isaacs A, van Duijn C, Witteman J. ACE polymorphisms.  Circ Res. 2006;  98 1123-1133
• 47 Seo JK, Ha SK, Park SH, Lee CH, Lee SY, Lee KC, Kim SJ, Park CH, Lee HY, Han DS. Association between ACE gene polymorphism and nephropathy in NIDDM patients.  Kor J Nephol. 1997;  16 469-481
• 48 Simoneau J-A, Bouchard C. Genetic determinism of fiber type proportion in human skeletal muscle.  FASEB J. 1995;  9 1091-1095
• 49 Song Y-H, Li W, Du J, Mitch WE, Rosenthal N, Delafontaine R. Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting.  J Clin Invest. 2005;  114 451-458
• 50 Thomis MA, Huygens W, Heuninckx S, Chagnon M, Maes HHM, Claessens AL, Vlietinck R, Bouchard C, Beunen GP. Exploration of myostatin polymorphisms and the angiotensin-converting enzyme insertion/deletion genotype in responses of human muscle to strength training.  Eur J Appl Physiol. 2004;  92 267-274
• 51 Tsianos G, Sanders J, Dhamrait S, Humphries S, Grant S, Montgomery HE. The ACE gene insertion/deletion polymorphism and elite endurance swimming.  Eur J Appl Physiol. 2004;  92 360-362
• 52 Williams AG, Rayson MP, Jubb M, World M, Woods DR, Hayward M, Martin J, Humphries SE, Montgomery HE. The ACE gene and muscle performance.  Nature. 2000;  403 614-615
• 53 Woods D, Hickman M, Jamshidi DB, Vassiliou V, Jones A, Humphries S, Montgomery HE. Elite swimmers and the D allele of the ACE I/D polymorphism.  Hum Genet. 2001;  108 230-232
• 54 Woods DR, Humphries SE, Montgomery HE. The ACE I/D polymorphism and human physical performance.  Trends Endocrinol Metab. 2000;  11 416-420
• 55 Woods D, Hickman M, Jamshidi Y, Brull D, Vassiliou V, Jones A, Humphries S, Montgomery H. Elite swimmers and the D allele of the ACE I/D polymorphism.  Hum Genet. 2001;  108 230-232
• 56 Xu H, Shete S. Effects of population structure on genetic association studies.  BMC Genet. 2005;  6 S109-S13
• 57 Zhao B, Moochhala SM, Tham S, Lu J, Chia M, Byrne C, Hu Q, Lee LKH. Relationship between angiotensin-converting enzyme ID polymorphism and VO_2max of Chinese males.  Life Sci. 2003;  73 2625-2630

Correspondence