Skip to main content
SpringerLink
Log in

Creatine kinase MM TaqI and methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms influence exercise-induced C-reactive protein levels

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. Results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CVD:

Cardiovascular disease

CAD:

Coronary artery disease

CK-MM:

Muscle-type creatine kinase

MTHFR:

Methylenetetrahydrofolate reductase

CK:

Creatine kinase

AST:

Aspartate aminotransferase

CRP:

C-reactive protein

hs-CRP:

High-sensitivity C-reactive protein

SNPs:

Single nucleotide polymorphisms

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

HWE:

Hardy–Weinberg equilibrium

ROS:

Reactive oxygen species

Hcy:

Homocysteine

References

  • Abbassi-Ghanavati M, Greer LG, Cunningham FG (2009) Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 114:1326–1331

    Article  PubMed  CAS  Google Scholar 

  • Akimoto AK, Miranda-Vilela AL, Alves PCZ, Pereira LCS, Lordelo GS, Hiragi CO, Silva ICR, Grisolia CK, Klautau-Guimarães MN (2010) Evaluation of gene polymorphisms in exercise-induced oxidative stress and damage. Free Rad Res 44:322–331

    Article  CAS  Google Scholar 

  • Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Bair TL, Madsen TE, Pearson RR (2000) Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation 102:1227

    PubMed  CAS  Google Scholar 

  • Apple FS, Rogers MA, Ivy JL (1986) Creatine kinase isoenzyme MM variants in skeletal muscle and plasma from marathon runners. Clin Chem 32:41–44

    PubMed  CAS  Google Scholar 

  • Araújo F, Pereira AC, Mota GF, Latorre Mdo R, Krieger JE, Mansur AJ (2004) The influence of tumor necrosis factor -308 and C-reactive protein G1059C gene variants on serum concentration of C-reactive protein: evidence for an age-dependent association. Clin Chim Acta 349(1–2):129–134

    Article  PubMed  Google Scholar 

  • Barbosa TM, Magalhães PM, Lopes VP, Neuparth M, Duarte JA (2003) Comparação da variação da actividade neuromuscular, da creatina quinase e da força isométrica máxima voluntária entre dois protocolos exaustivos e inabituais. Rev Port Cien Desp 3:7–15

    Google Scholar 

  • Benedini S, Caimi A, Alberti G, Terruzzi I, Dellerma N, La Torre A, Luzi L (2010) Increase in homocysteine levels after a half-marathon running: a detrimental metabolic effect of sport? Sport Sci Health 1:35–42

    Article  Google Scholar 

  • Biselli PM, Guerzoni AR, Goloni-Bertollo EM, de Godoy MF, Abou-Chahla JAB, Pavarino-Bertelli EC (2009) Variabilidade genética MTHFR no desenvolvimento da doença arterial coronária. Rev Assoc Med Bras 55:274–278

    Article  PubMed  Google Scholar 

  • Borrione P, Rizzo M, Spaccamiglio A, Salvo RA, Dovio A, Termine A, Parisi A, Fagnani F, Angeli A, Pigozzi F (2008) Sport-related hyperhomocysteinaemia: a putative marker of muscular demand to be noted for cardiovascular risk. Br J Sports Med 42:894–900

    Article  PubMed  CAS  Google Scholar 

  • Bouchard C, Malina RM, Pérusse L (1997) Genetics of fitness and physical performance. Human Kinetics, Champaign, IL

    Google Scholar 

  • Brancaccio P, Maffulli N, Limongelli FM (2007) Creatine kinase monitoring in sport medicine. Br Med Bull 81(82):209–230

    Article  PubMed  Google Scholar 

  • Bruce R, Todd JK, Le Dune L (1958) Serum transaminase: its clinical use in diagnosis and prognosis. Br Med J 2:1125–1128

    Article  PubMed  CAS  Google Scholar 

  • Brull DJ, Serrano N, Zito F, Jones L, Montgomery HE, Rumley A, Sharma P, Lowe GDO, World MJ, Humphries SE, Hingorani AD (2003) Human CRP gene polymorphism influences CRP levels: implications for the prediction and pathogenesis of coronary heart disease. Arterioscler Thromb Vasc Biol 23:2063–2069

    Article  PubMed  CAS  Google Scholar 

  • Cao H, Hegele RA (2000) Human C-reactive protein (CRP) 1059G/C polymorphism. J Hum Genet 45:100–101

    Article  PubMed  CAS  Google Scholar 

  • Carlson DL, Mawdsley RH (1986) Sports anemia: a review of the literature. Am J Sports Med 14:109–112

    Article  PubMed  CAS  Google Scholar 

  • Cortese C, Motti C (2001) MTHFR gene polymorphism, homocysteine and cardiovascular Disease. Public Health Nutr 4:493–497

    Article  PubMed  CAS  Google Scholar 

  • Cruzat VF, Rogero MM, Borges MC, Tirapegui J (2007) Aspectos atuais sobre estresse oxidativo, exercícios físicos e suplementação. Rev Bras Med Esp 13(5):336–342

    Article  Google Scholar 

  • Dedoussis GV, Panagiotakos DB, Pitsavos C, Chrysohoou C, Skoumas J, Choumerianou D, Stefanadis C, ATTICA Study Group (2005) An association between the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and inflammation markers related to cardiovascular disease. Int J Cardiol 100(3):409–414

    Article  PubMed  Google Scholar 

  • Defoor J, Martens K, Matthijs G, Zieliñska D, Schepers D, Philips T, Vlietinck R, Fagard R, Vanhees L (2005) The CAREGENE Study: muscle-specific creatine kinase gene and aerobic power in coronary artery disease. Eur J Cardiovasc Prev Rehabil 12:415–417

    Article  PubMed  Google Scholar 

  • Dewar HA, Rowell NR, Smith AJ (1958) Serum glutamic oxalacetic transaminase in acute myocardial infarction. Br Med J 2:1121–1125

    Article  PubMed  CAS  Google Scholar 

  • Dufaux B, Order U, Geyer H, Hollmann W (1984) C-reactive protein serum concentrations in well-trained athletes. Int J Sports Med 5(2):102–106

    Article  PubMed  CAS  Google Scholar 

  • Eikelboom JW, Lonn E, Genest J, Hankey G, Yusuf F (1999) Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 131:363–375

    PubMed  CAS  Google Scholar 

  • Ferreira F, Ferreira R, Duarte JA (2007) Stress oxidativo e dano oxidativo muscular esquelético: influência do exercício agudo inabitual e do treino físico. Rev Port Cien Desp 7(2):257–275

    Google Scholar 

  • Fortunato G, Fattoruso O, De Caterina M, Mancini A, Di Fiore R, Alfieri A, Tafuri D, Buono P (2007) RAS and MTHFR gene polymorphisms in a healthy exercise-trained population: association with the MTHFR (TT) genotype and a lower hemoglobin level. Int J Sports Med 28(2):172–177

    Article  PubMed  CAS  Google Scholar 

  • Foschini D, Prestes J, Charro MA (2007) Relação entre exercício físico, dano muscular e dor muscular de início tardio. Rev Bras Cineantropom Desempenho Hum 9:101–106

    Google Scholar 

  • Freire LMD, Sodré FL, Oliveira RA, Castilho LN, Faria EC (2008) Controle de qualidade laboratorial pré-analítico: avaliação de solicitações médicas de exames bioquímicos no Hospital de Clínicas da Universidade Estadual de Campinas, São Paulo, Brasil. Rev Bras Anal Clin 40:143–145

    Google Scholar 

  • Fujimura H, Kawasaki T, Sakata T, Ariyoshi H, Kato H, Monden M, Miyata T (2000) Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia. Thromb Res 98(1):1–8

    Article  PubMed  CAS  Google Scholar 

  • Graham IM, Daly LE, Refsum HM, Robinson K, Brattstrom LE, Ueland PM, Palma-Reis RJ, Boers GH, Sheahan RG, Israelsson B, Uiterwaal CS, Melead R, McMaster D, Verhoef P, Witteman J, Rubba P, Bellet H, Wautrecht JC, de Valk HW, Sales Luis AC, Parrot-Roulaud FM, Tan KS, Higgins I, Garcon D, Medrano MJ, Candito M, Evans AE, Andria G (1997) Plasma homocysteine as a risk factor for cardiovascular disease: the European concerted action project. J Am Med Assoc 277:1775–1781

    Article  CAS  Google Scholar 

  • Griffiths PD (1964) Serum levels of creatine phosphokinase. J Clin Pathol 17:56–57

    Article  PubMed  CAS  Google Scholar 

  • Heled Y, Bloom MS, Wu TJ, Stephens Q, Deuster PA (2007) CM-MM and ACE genotypes and physiological prediction of the creatine kinase response to exercise. J Appl Physiol 103:504–510

    Article  PubMed  CAS  Google Scholar 

  • Hornemann T, Kempa S, Himmel M, Hayess K, Fürst DO, Wallimann T (2003) Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein. J Mol Biol 332:877–887

    Article  PubMed  CAS  Google Scholar 

  • Ji LL, Leichtweis S (1997) Exercise and oxidative stress: sources of free radicals and their impact on antioxidant systems. Age 20:91–106

    Article  CAS  Google Scholar 

  • Judge S, Leeuwenburgh C (2007) Cardiac mitochondrial bioenergetics, oxidative stress, and aging. Am J Physiol Cell Physiol 292:1983–1992

    Article  Google Scholar 

  • Kang S-S, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N (1991) Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 48:536–645

    PubMed  CAS  Google Scholar 

  • Kasapis C, Thompson PD (2005) The effects of physical activity on serum C-reactive protein and inflammatory markers. J Am Coll Cardiol 45(10):1563–1569

    Article  PubMed  CAS  Google Scholar 

  • Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  PubMed  CAS  Google Scholar 

  • MacArthur DG, North KN (2005) Genes and human elite athletic performance. Hum Genet 116:331–339

    Article  PubMed  CAS  Google Scholar 

  • Miller DT, Zee RY, Suk DJ, Kozlowski P, Chasman DI, Lazarus R, Cook NR, Ridker PM, Kwiatkowski DJ (2005) Association of common CRP gene variants with CRP levels and cardiovascular events. Ann Hum Genet 69:623–638

    Article  PubMed  CAS  Google Scholar 

  • Miranda-Vilela AL, Akimoto AK, Alves PCZ, Pereira LCS, Gonçalves CA, Klautau-Guimarães MN, Grisolia CK (2009) Dietary carotenoid-rich oil improves plasma lipid peroxidation and damages in runners: evidence for an association with MnSOD genetic variant –Val9Ala. Genet Mol Res 8:1481–1495

    Article  PubMed  CAS  Google Scholar 

  • Misawa AK, Suzuki H, Maia Júnior OO, Bonanomi MTBC, Melo CSN (2008) Obstrução arterial retiniana periférica associada com hiperhomocisteinemia: relato de caso. Arq Bras Oftalmol 71(5):729–733

    Article  PubMed  Google Scholar 

  • Montaner J, Fernandez-Cadenas I, Molina CA, Ribó M, Huertas R, Rosell A, Penalba A, Ortega L, Chacón P, Alvarez-Sabín J (2006) Poststroke C-reactive protein is a powerful prognostic tool among candidates for thrombolysis. Stroke 37(5):1205–1210

    Article  PubMed  CAS  Google Scholar 

  • Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Sindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T, Suzuki S, Yazaki Y (1997) Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 95:2032–2036

    PubMed  CAS  Google Scholar 

  • Mougios V (2007) Reference intervals for serum creatine kinase in athletes. Br J Sports Med 41:674–678

    Article  PubMed  Google Scholar 

  • Nascimben L, Ingwall JS, Pauletto P, Friedrich J, Gwathmey JK, Saks V, Pessina AC, Allen PD (1996) Creatine kinase system in failing and nonfailing human myocardium. Circulation 94:1894–1901

    PubMed  CAS  Google Scholar 

  • Ostrander EA, Huson HJ, Ostrander GK (2009) Genetics of athletic performance. Annu Rev Genomics Hum Genet 10:407–429

    Article  PubMed  CAS  Google Scholar 

  • Persky AM, Green PS, Stubley L, Howell CO, Zaulyanov L, Brazeau GA, Simpkins JW (2000) Protective effect of estrogens against oxidative damage to heart and skeletal muscle in vivo and in vitro. Proc Soc Exp Biol Med 223:59–66

    Article  PubMed  CAS  Google Scholar 

  • Putney S, Herlihy W, Royal N, Pang H, Aposhian HV, Pickering L, Belagaje R, Biemann K, Page D, Kuby S, Schimmel P (1984) Rabbit muscle creatine phosphokinase. J Biol Chem 259:14317–14320

    PubMed  CAS  Google Scholar 

  • Radak Z, Kumagai S, Nakamoto H, Asto S (2007) 8-Oxoguanosine and uracil repair of nuclear and mitochondrial DNA in red and white skeletal muscle of exercise-trained old rats. J Appl Physiol 102:1696–1701

    Article  PubMed  CAS  Google Scholar 

  • Rankinen T, Wolfarth B, Simoneau J-A, Maier-Lenz D, Rauramaa R, Rivera MA, Boulay MR, Chagnon YC, Pérusse L, Keul J, Bouchard C (2000) No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status. J Appl Physiol 88:1571–1575

    PubMed  CAS  Google Scholar 

  • Rifai N, Ridker PM (2003) Population distributions of C-reactive protein in apparently healthy men and women in the United States: implication for clinical interpretation. Clin Chem 49(4):666–669

    Article  PubMed  CAS  Google Scholar 

  • Rifai N, Tracy RP, Ridker PM (1999) Clinical efficacy of an automated high-sensitivity C-reactive protein assay. Clin Chem 45(12):2136–2141

    PubMed  CAS  Google Scholar 

  • Rivera MA, Dionne FT, Wolfarth B, Chagnon M, Simoneau J-A, Pérusse L, Boulay MR, Gagnon J, Song TMK, Keul J, Bouchard C (1997) Muscle-specific creatine kinase gene polymorphisms in elite endurance athletes and sedentary controls. Med Sci Sports Exerc 29:1444–1447

    Article  PubMed  CAS  Google Scholar 

  • Santos-Silva A, Rebelo MI, Castro EM, Belo L, Guerra A, Rego C, Quintanilha A (2001) Leukocyte activation, erythrocyte damage, lipid profile and oxidative stress imposed by high competition physical exercise in adolescents. Clin Chim Acta 306:119–126

    Article  PubMed  CAS  Google Scholar 

  • Schoenfelder M (2010) Genetics-based performance talent research: polymorphisms as predictors of endurance performance. J Appl Physiol 108:1454–1455

    Article  PubMed  CAS  Google Scholar 

  • Schumann G, Klauke R (2003) New IFCC reference procedures for the determination of catalytic activity concentrations of five enzymes in serum: preliminary upper reference limits obtained in hospitalized subjects. Clin Chim Acta 327:69–79

    Article  PubMed  CAS  Google Scholar 

  • Suk HJ, Ridker PM, Cook NR, Zee RYL (2005) Relation of polymorphism within the C-reactive protein gene and plasma CRP levels. Atherosclerosis 178:139–145

    Article  PubMed  CAS  Google Scholar 

  • Sureda A, Tauler P, Aguiló A, Cases N, Fuentespina E, Córdova A, Tur JA, Pons A (2005) Relation between oxidative stress markers and antioxidant endogenous defences during exhaustive exercise. Free Rad Res 39:1317–1324

    Article  CAS  Google Scholar 

  • Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado D, Estes NAM, Fulton JE, Gordon N, Haskell WL, Link MS, Maron BJ, Mittleman MA, Pelliccia A, Wenger NK, Willich SN, Costa F (2007) Exercise and acute cardiovascular events. Circulation 115:2358–2368

    Article  PubMed  Google Scholar 

  • Traber MG (2006) Relationship of vitamin E metabolism and oxidation in exercising human subjects. Br J Nutr 96:S34–S37

    Article  PubMed  CAS  Google Scholar 

  • Urso ML, Clarkson PM (2003) Oxidative stress, exercise, and antioxidant supplementation. Toxicology 189:41–54

    Article  PubMed  CAS  Google Scholar 

  • van Bockxmeer FM, Mamotte CDS, Vasikaran SD, Taylor RR (1997) Methylenetetrahydrofolate reductase gene and coronary artery disease. Circulation 95:21–23

    PubMed  Google Scholar 

  • Yi P, Pogribny IP, James SJ (2002) Multiplex PCR for simultaneous detection of 677 C→T and 1298 A→C polymorphisms in methylenetetrahydrofolate reductase gene for population studies of cancer risk. Cancer Lett 181:209–213

    Article  PubMed  CAS  Google Scholar 

  • Zhou DQ, Hu Y, Liu G, Wu J, Gong L (2005) An A/G polymorphism in muscle-specific creatine kinase gene in Han population in northern China. Yi Chuan 27:535–538

    PubMed  CAS  Google Scholar 

  • Zhou DQ, Hu Y, Liu G, Gong L, Xi Y, Wen L (2006) Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme. Br J Sports Med 40:988–991

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the subjects who participated in this research, Sabin Institute/Sabin Laboratories and Farmacotécnica for technical support. They also thank the National Council for Technological and Scientific Development (CNPq), the Coordination for Further Training of Graduate Staff (CAPES) and the Scientific and Technological Enterprises Foundation (FINATEC) for financial support.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Laboratório de Genética, Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brazil

    Ana Luisa Miranda-Vilela, Arthur K. Akimoto, Graciana S. Lordelo, Cesar K. Grisolia & Maria de Nazaré Klautau-Guimarães

  2. Laboratório Sabin de Análises Clínicas, Brasília, DF, Brazil

    Luiz C. S. Pereira

Authors
  1. Ana Luisa Miranda-Vilela
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arthur K. Akimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graciana S. Lordelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luiz C. S. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cesar K. Grisolia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria de Nazaré Klautau-Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Luisa Miranda-Vilela.

Additional information

Communicated by Martin Flueck.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miranda-Vilela, A.L., Akimoto, A.K., Lordelo, G.S. et al. Creatine kinase MM TaqI and methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms influence exercise-induced C-reactive protein levels. Eur J Appl Physiol 112, 183–192 (2012). https://doi.org/10.1007/s00421-011-1967-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-011-1967-3

Keywords

Search

Navigation