Is the C34T Polymorphism of the AMPD1 Gene Associated with Athlete Performance in Rowing?

P. Ciȩszczyk; J. Eider; M. Ostanek; A. Leońska-Duniec; K. Ficek; K. Kotarska; G. Girdauskas

doi:10.1055/s-0031-1283186

International Journal of Sports Medicine, Table of Contents

Int J Sports Med 2011; 32(12): 987-991
DOI: 10.1055/s-0031-1283186

Genetics & Molecular Biology

Is the C34T Polymorphism of the AMPD1 Gene Associated with Athlete Performance in Rowing?

Authors

P. Ciȩszczyk

¹Institute of Physical Culture, University of Szczecin, Poland
J. Eider

²Faculty of Physical Culture and Health Promotion, University of Szczecin, Poland
M. Ostanek

³Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Poland
A. Leońska-Duniec

⁴Department of Genetics, University of Szczecin, Poland
K. Ficek

⁵Department of Health, Galen Medical Center, Bierun, Poland
K. Kotarska

²Faculty of Physical Culture and Health Promotion, University of Szczecin, Poland
G. Girdauskas

⁶Faculty of Team Sports, Lithuanian Academy of Physical Education, Kaunas, Lithuania

Abstract

The skeletal muscle-specific isoform of adenosine monophosphate deaminase (AMPD) is one of the most important regulators of muscle energy metabolism. A nonsense C to T transition in nucleotide 34 (C34T) in exon 2 of AMPD1 gene converts the codon CAA into the premature stop-codon TAA. 127 Polish male rowers including Olympic and world champions were recruited for this study. Controls samples were obtained from 251 unrelated volunteers. Statistically significant differences in genotype distribution were observed when only a whole group of rowers (88.19% CC, 11.81% CT, 0% TT; p=0.009) were compared with controls (75.31% CC, 23.10% CT, 1,59% TT). A significant deficiency of the T allele compared to control samples was noted in the elite rowers (4.55%, p=0.021) and non-elite rowers (6.63%, p=0.023), whereas this trend was even stronger when compared with the controls for the whole group of rowers (5.91%, p=0.002). Our results suggest that the T allele is associated with physical performance level, therefore, it may be included in the group of performance altering polymorphisms as a negative factor to athletic performance.

Key words

AMPD - genotype - rowing - athlete performance

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References

References
1 Ahmetov II, Williams AG, Popov DV, Lyubaeva EV, Hakimullina AM, Fedotovskaya ON, Mozhayskaya IA, Vinogradova OL, Astratenkova IV, Montgomery HE, Rogozkin VA. The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes. Hum Genet 2009; 126: 751-761
2 Broberg S, Sahlin K. Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol 1989; 67: 116-122
3 Cooke R, Pate E. The effects of ADP and phosphate on the contraction of muscle fibers. Biophys J 1985; 48: 789-98
4 De Ruiter CJ, May AM, van Engelen BG, Wevers RA, Steenbergen-Spanjers GC, de Haan A. Muscle function during repetitive moderate-intensity muscle contractions in myoadenylate deaminase-deficient Dutch subjects. Clin Sci 2002; 102: 531-539
5 Dudley GA, Staron RS, Murray TF, Hagerman FC, Luginbuhl A. Muscle fiber composition and blood ammonia levels after intense exercise in humans. J Appl Physiol 1983; 54: 582-586
6 Eynon N, Meckel Y, Alves AJ, Nemet D, Eliakim D. Is there an interaction between BDKRB2 − 9/+9 and GNB3 C825T polymorphisms and elite athletic performance?. Scand J Med Sci Sports 2011; Jan 7 [Epub ahead of print]
7 Fishbein WN, Armbrustmacher VW, Griffin JL. Myoadenylate deaminase deficiency: a new disease of muscle. Science 1978; 200: 545-548
8 Fishbein WN, Foellmer JW, Davis JI. Medical implications of the lactate and ammonia relationship in anaerobic exercise. Int J Sports Med 1990; 11: 91-100
9 Fischer H, Esbjornsson M, Sabina RL, Stromberg A, Peyrard-Janvid M, Norman B. AMP deaminase deficiency is associated with lower sprint cycling performance in healthy subjects. J Appl Physiol 2007; 103: 315-322
10 Gross M. Molecular biology of AMP deaminase deficiency. Pharm World Sci 1994; 16: 55-61
11 Gross M. Clinical heterogeneity and molecular mechanisms in inborn muscle AMP deaminase deficiency. J Inherit Metab Dis 1997; 20: 186-192
12 Harriss DJ, Atkinson G. Update – Ethical Standards in Sport and Exercise Science Research. Int J Sports Med 2011; 32: 819-821
13 Lowenstein JM. The purine nucleotide cycle revised. Int J Sports Med 1990; 11: 37-46
14 Lucia A, Martin MA, Esteve-Lanao J, San Juan AF, Rubio JC, Oliván J, Arenas J. C34T mutation of the AMPD1 gene in an elite white runner. Br J Sports Med 2006; 40: e7
15 Meckel Y, Nemet D, Alves AJ, Eliakim A, Eynon N. AMPD1 C34T Mutation is not associated with the status of Israeli athletes. Eur J Sport Sci. [in press]
16 Morisaki T, Gross M, Morisaki H, Pongratz D, Zöllner N, Holmes EW. Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci USA 1992; 89: 6457-6461
17 Morisaki T, Sabina RL, Holmes EW. Adenylate deaminase. A multigene family in humans and rats. J Biol Chem 1990; 265: 11482-11486
18 Muniesa CA, Gonzalez-Freire M, Santiago C, Lao JI, Buxens A, Rubio JC, Martin MA, Arenas J, Gomez-Gallego F, Lucia A. World-class performance in lightweight rowing: is it genetically influenced? A comparison with cyclists, runners and non-athletes. Br J Sports Med 2008; 44: 898-901
19 Norman B, Mahnke-Zizelman DK, Vallis A, Sabina RL. Genetic and other determinants of AMP deaminase activity in healthy adult skeletal muscle. J Appl Physiol 1998; 85: 1273-1278
20 Norman B, Sollevi A, Jansson E. Increased IMP content in glycogen-depleted muscle fibres during submaximal exercise in man. ActaPhysiol Scand 1988; 133: 97-100
21 Rico-Sanz J, Rankinen T, Joanisse DR, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Associations between cardiorespiratory responses to exercise and the C34T AMPD1 gene polymorphism in the HERITAGE Family study. Physiol Genomics 2003; 14: 161-166
22 Rubio JC, Martın MA, Rabadan M, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Frequency of the C34T mutation of the AMPD1 gene in world-class endurance athletes: does this mutation impair performance?. J Appl Physiol 2005; 98: 2108-2112
23 Rubio JC, Pérez M, Maté-Muñoz JL, García-Consuegra I, Chamorro-Viña C, Fernández del Valle M, Andreu AL, Martín MA, Arenas J, Lucia A. AMPD1 genotypes and exercise capacity in McArdle patients. Int J Sports Med 2008; 29: 331-335
24 Sabina RL, Holmes EW. Myoadenylate deaminase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Vale D. (eds) The Metabolic and Molecular Basis of Inherited Disease. New York: McGraw-Hill; 2001: 2627-2638
25 Sabina RL, Morisaki T, Clarke P, Eddy R, Shows TB, Morton CC, Holmes EW. Characterization of the human and rat myoadenylate deaminase genes. J Biol Chem 1990; 265: 9423-9433
26 Sabina RL, Swain JL, Olanow CW, Bradley WG, Fishbein WN, DiMauro S, Holmes EW. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle. J Clin Invest 1984; 73: 720-730
27 Safronow K, Czyzycka E, Binczak-Kuleta A, Rzeuski R, Skowronek J, Wojtarowicz A, Jakubowska K, Olszewska M, Loniewska B, Kaliszczak R, Kornacewicz-Jach Z, Ciechanowicz A, Chlubek D. Association of C34T AMPD1 gene polymorphism with features of patients with coronary artery disease or heart failure. Scand J Clin Lab Investig 2009; 69: 102-112
28 Safranow K, Suchy J, Jakubowska K, Olszewska M, Bińczak-Kuleta A, Kurzawski G, Rzeuski R, Czyżycka E, Łoniewska B, Kornacewicz-Jach Z, Ciechanowicz A, Chlubek D. AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases. J Appl Genetics 2011; 52: 67-76
29 Sahlin K, Katz A, Broberg S. Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am J Physiol Cell Physiol 1990; 259: 834-841
30 Santiago CJ, Ruiz R, Muniesal CA, Gonzalez-Freire M, Gomez-Gallego F, Lucial A. Does the polygenic profile determine the potential for becoming a world-class athlete? Insights from the sport of rowing. Scand J Med Sci Sports 2010; 20: e188-e194
31 Secher NH. Physiological and biomechanical aspects of rowing. Implications for training. Sports Med 1993; 15: 24-42
32 Sinkeler SP, Binkhorst RA, Joosten EM, Wevers RA, Coerwinkei MM, Oei TL. AMP deaminase deficiency: study of the human skeletal muscle purine metabolism during ischemic isometric exercise. Clin Science 1987; 72: 475-482
33 Spencer MK, Yan Z, Katz A. Effect of low glycogen on carbohydrate and energy metabolism in human muscle during exercise. Am J Physiol Cell Physiol 1992; 262: 975-979
34 Tarnopolsky MA, Parise G, Gibala MJ, Graham TE, Rush JWE. Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans. J Physiol 2001; 533: 881-889
35 Verzijl HT, van Engelen BG, Luyten JA, Steenbergen GC, van den Heuvel LP, ter Laak HJ, Padberg GW, Wevers RA. Genetic characteristics of myoadenylate deaminase deficiency. Ann Neurol 1998; 44: 140-143
36 Westerblad H, Dahlstedt AJ, Lannergren J. Mechanisms underlying reduced maximum shortening velocity during fatigue of intact, single fibers of mouse muscle. J Physiol 1998; 510: 269-277