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Int J Sports Med 2008; 29(4): 331-335
DOI: 10.1055/s-2007-965358
Clinical Sciences

© Georg Thieme Verlag KG Stuttgart · New York

AMPD1 Genotypes and Exercise Capacity in McArdle Patients

J. C. Rubio1 , 2 , M. Pérez3 , J. L. Maté-Muñoz3 , I. García-Consuegra1 , 2 , C. Chamorro-Viña3 , M. Fernández del Valle3 , A. L. Andreu2 , 4 , M. A. Martín1 , 2 , J. Arenas1 , 2 , A. Lucia3
  • 1Centro de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain
  • 2Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)
  • 3Physiology, Universidad Europea de Madrid, Madrid, Spain
  • 4Research Centre in Biochemistry and Molecular Biology, Hospital Vall d'Hebron, Barcelona, Spain
Further Information

Publication History

accepted after revision March 10, 2007

Publication Date:
09 August 2007 (online)

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Abstract

The purpose of this study was to assess if there exists an association between C34T muscle adenosine monophosphate deaminase (AMPD1) genotypes (i.e., normal homyzygotes [CC] vs. heterozygotes [CT]) and directly measured indices of exercise capacity (peak oxygen uptake [V·O2peak], ventilatory threshold [VT], gross mechanical efficiency [GE], etc.) in 44 Caucasian McArdle patients (23 males, 21 females). All patients performed a graded cycle ergometer test until exhaustion (for V·O2peak and VT determination) and a 12-min constant-load test at the power output eliciting the VT (for GE determination). We found no significant difference in indices of exercise capacity between CC (n = 18) and CT genotypes (n = 5) in the group of male patients (p > 0.05). In contrast, the V·O2 at the VT was significantly lower (p < 0.05) in CT (n = 4; 7.9 ± 0.4 ml/kg/min) than in CC female patients (n = 17; 11.0 ± 0.9 ml/kg/min). In summary, heterozigosity for the C34T allele of the AMPD gene is associated with reduced submaximal aerobic capacity in female patients with McArdle disease and might partly account, in this gender, for the variability that exists in the phenotypic manifestation of the disease.

Key words

glycogenosis type V - AMP deaminase - ventilatory threshold - V·O2peak

References

  • 1 Bruno C, Cassandrini D, Martinuzzi A, Toscano A, Moggio M, Morandi L, Servidei S, Mongini T, Angelini C, Musumeci O, Comi G P, Lamperti C, Filosto M, Zara F, Minetti C. McArdle disease: the mutation spectrum of PYGM in a large Italian cohort.  Hum Mutat. 2006;  27 718
    PubMedSearch in Google Scholar
  • 2 Burki N K, Alam M, Lee L-Y. The pulmonary effects of intravenous adenosine in asthmatic subjects.  Respir Res. 2006;  30 (7) 139
    PubMedSearch in Google Scholar
  • 3 Burki N K, Dale W J, Lee L-Y. Intravenous adenosine and dyspnea in man.  J Appl Physiol. 2005;  98 180-185
    PubMedSearch in Google Scholar
  • 4 Chavarren J, Calbet J AL. Cycling efficiency and pedalling frequency in road cyclists.  Eur J Appl Physiol. 1999;  80 555-563
    CrossrefPubMedSearch in Google Scholar
  • 5 Coleridge J C, Coleridge H M. Afferent vagal C fibre innervation of the lungs and airways and its functional significance.  Rev Physiol Biochem Pharmacol. 1984;  99 1-110
    PubMedSearch in Google Scholar
  • 6 Engelstein E D, Lerman B B, Somers V K, Rea R F. Role of arterial chemoreceptors in mediating the effects of endogenous adenosine on sympathetic nerve activity.  Circulation. 1994;  90 2919-2926
    PubMedSearch in Google Scholar
  • 7 Gitt A K, Wasserman K, Kilkowski C, Kleemann T, Kilkowski A, Bangert M, Schneider S, Schwarz A, Senges J. Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death.  Circulation. 2002;  10 3079-3084
    PubMedSearch in Google Scholar
  • 8 Griffiths T L, Warren S J, Chant A D, Holgate S T. Ventilatory effects of hypoxia and adenosine infusion in patients after bilateral carotid endarterectomy.  Clin Sci. 1990;  78 25-31
    PubMedSearch in Google Scholar
  • 9 Gross M, Rotzer E, Kolle P, Mortier W, Reichmann H, Goebel H H, Lochmuller H, Pongratz D, Mahnke-Zizelman D K, Sabina R L. G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population.  Neuromuscul Disord. 2002;  12 558-565
    PubMedSearch in Google Scholar
  • 10 Hagberg J M, Coyle E F, Carroll J E, Miller J M, Martin W H, Brooke M H. Exercise hyperventilation in patients with McArdle's disease.  J Appl Physiol. 1982;  52 991-994
    PubMedSearch in Google Scholar
  • 11 Hagberg J M, King D S, Rogers M A, Mountain S J, Jilka S M, Kohrt W M, Heller S L. Exercise and recovery ventilatory and V·O2 responses of patients with McArdle's disease.  J Appl Physiol. 1990;  68 1393-1398
    PubMedSearch in Google Scholar
  • 12 Heller S L, Kaiser K K, Planer G L, Hagberg J M, Brooke M H. McArdle's disease with myoadenylate deaminase deficiency: observations in a combined enzyme deficiency.  Neurology. 1987;  37 1039-1042
    PubMedSearch in Google Scholar
  • 13 Koike A M, Hiroe M, Adachi H, Yajima T, Nogami A, Ito H, Takamoto T, Taniguchi K, Marumo F. Anaerobic metabolism as an indicator of aerobic function during exercise in cardiac patients.  J Am Coll Cardiol. 1992;  20 120-126
    PubMedSearch in Google Scholar
  • 14 Lowenstein J M. Ammonia production in muscle and other tissues: the purine nucleotide cycle.  Physiol Rev. 1972;  52 382-414
    PubMedSearch in Google Scholar
  • 15 Lucia A, Hoyos J, Santalla A, Earnest C, Chicharro J L. Tour de France vs. Vuelta a España: which is harder?.  Med Sci Sports Exerc. 2003;  35 872-878
    CrossrefPubMedSearch in Google Scholar
  • 16 Lucia A, Maté-Muñoz J L, Pérez M, Gutierrez-Rivas E, Foster C, Arenas J. Double trouble (McArdle's disease and myasthenia gravis): how can exercise help?.  Muscle Nerve. 2007;  35 125-128
    CrossrefPubMedSearch in Google Scholar
  • 17 Martin M A, Rubio J C, Buchbinder J, Fernandez-Hojas R, del Hoyo P, Teijeira S, Gámez J, Navarro C, Fernández J M, Cabello A, Campos Y, Cervera C, Culebras J M, Andreu A L, Fletterick R, Arenas J. Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotype-phenotype correlation study.  Ann Neurol. 2001;  50 574-581
    CrossrefPubMedSearch in Google Scholar
  • 18 Martinuzzi A, Sartori E, Fanin M, Nascimbeni A, Valente L, Angelini C, Siciliano G, Mongini T, Tonin P, Tomelleri G, Toscano A, Merlini L, Bindoff L A, Bertelli S. Phenotype modulators in myophosphorylase deficiency.  Ann Neurol. 2003;  53 497-502
    CrossrefPubMedSearch in Google Scholar
  • 19 Matsumura N, Nishijima H, Kojima S, Hashimoto F, Minami M, Yasuda H. Determination of anaerobic threshold for assessment of functional state in patients with chronic heart failure.  Circulation. 1983;  68 360-367
    PubMedSearch in Google Scholar
  • 20 Maxwell D L, Fuller R W, Nolop K B, Dixon C M, Hughes J M. Effects of adenosine on ventilatory responses to hypoxia and hypercapnia in humans.  J Appl Physiol. 1986;  61 1762-1766
    PubMedSearch in Google Scholar
  • 21 McArdle B. Myophaty due to a defect in muscle glycogen breakdown.  Clin Sci. 1951;  10 13-33
    PubMedSearch in Google Scholar
  • 22 Meyer T, Lucia A, Earnest C P, Kindermann W. A conceptual framework for performance diagnosis and training prescription from submaximal gas exchange parameters - theory and application.  Int J Sports Med. 2005;  26 (Suppl 1) S38-S48
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Morisaki T, Gross M, Morisaki H, Pongratz D, Zollner N, Holmes E W. Molecular basis of AMP deaminase deficiency in skeletal muscle.  Proc Natl Acad Sci USA. 1992;  89 6457-6661
    CrossrefPubMedSearch in Google Scholar
  • 24 Norman B, Glenmark B, Jansson E. Muscle AMP deaminase deficiency in 2 % of healthy population.  Muscle Nerve. 1995;  18 239-241
    CrossrefPubMedSearch in Google Scholar
  • 25 Norman B, Sabina R L, Jansson E. Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects.  J Appl Physiol. 2001;  91 258-264
    PubMedSearch in Google Scholar
  • 26 Pérez M, Martin M A, Cañete S, Rubio J C, Fernández-Moreira D, San Juan A F, Gómez-Gallego F, Santiago C, Arenas J, Lucia A. Does the C34T mutation in AMPD1 alter exercise capacity in the elderly?.  Int J Sports Med. 2006;  27 429-435
    Thieme ConnectPubMedSearch in Google Scholar
  • 27 Pérez M, Martin M A, Rubio J C, Maté-Muñoz J L, Gómez-Gallego F, Foster C, Andreu A L, Arenas J, Lucia A. Exercise capacity in a 78 year old patient with McArdle's disease: it is never too late to start exercising.  Br J Sports Med. 2006;  40 725-726
    CrossrefPubMedSearch in Google Scholar
  • 28 Rico-Sanz J, Rankinen T, Joanisse D R, Leon A S, Skinner J S, Wilmore J H, Rao D C, 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
    CrossrefPubMedSearch in Google Scholar
  • 29 Riley M, Nicholls D P, Nugent A-M, Steele I C, Bell N, Davies P M, Stanford C F, Patterson V H. Respiratory gas exchange and metabolic responses during exercise in McArdle's disease.  J Appl Physiol. 1993;  75 745-754
    PubMedSearch in Google Scholar
  • 30 Rubio J C, Martin M A, Del hoyo P, Bautista J, Campos Y, Segura D, Navarro C, Ricoy J R, Cabello A, Arenas J. Molecular analysis of Spanish patients with AMP deaminase deficiency.  Muscle Nerve. 2000;  23 1175-1178
    PubMedSearch in Google Scholar
  • 31 Rubio J C, Nogales-Gadea G, Garcia-Consuegra I, Blázquez A, Cabello A, Lucia A, Andreu A L, Arenas J, Martin M A. A proposed molecular diagnosis flowchart for myophopshorylase deficiency (McArdle disease) in blood samples from Spanish patients.  Hum Mutat. 2007;  28 203-204
    PubMedSearch in Google Scholar
  • 32 Tarnopolsky M A, Parise G, Gibala M J, Graham T E, Rush J W. Myoadenylate deaminase deficiency does not affect muscle anaplerosis during exhaustive exercise in humans.  J Physiol. 2001;  533 881-889
    CrossrefPubMedSearch in Google Scholar
  • 33 Tsujino S, Shanske S, Dimauro S. Molecular genetic heterogeneity of myophosphorylase deficiency (McArdle disease).  N Engl J Med. 1993;  329 241-245
    CrossrefPubMedSearch in Google Scholar
  • 34 Vissing J, Haller R G. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease.  N Engl J Med. 2003;  349 2503-2509
    CrossrefPubMedSearch in Google Scholar
  • 35 Winder W W. Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle.  J Appl Physiol. 2001;  91 1017-1028
    PubMedSearch in Google Scholar

Prof. Alejandro Lucia

Physiology
Universidad Europea de Madrid

Villaviciosa de Odón

28670 Madrid

Spain

Phone: + 34 9 16 64 78 00

Fax: + 34 9 16 16 82 65

Email: alejandro.lucia@uem.es