Abstract
The NOS3 gene is a candidate to explain individual variations in health and exercise related phenotypes. We compared genotypic and allelic frequencies of the NOS3 −786 T/C polymorphism (rs2070744) in three groups of men of the same Caucasian (Spanish) descent: (i) elite endurance athletes (cyclists, runners; N = 100); (ii) elite power athletes (jumpers, throwers, sprinters; N = 53) and (iii) non-athletic controls (N = 100). The frequency of the TT genotype was significantly higher in power athletes (57%) than in the endurance (33%, P = 0.017) or control group (34%, P = 0.026). The frequency of the T allele was also higher in power sportsmen (71%) than in their endurance (55%, P = 0.003) and control referents (56%, P = 0.015). No differences were observed between control and endurance groups. In summary, the −786 T/C polymorphism of the NOS3 gene seems to be associated with elite performance in power-oriented athletic events (throwing, jumping, sprinting), with the T allele exerting a beneficial effect. The mechanism by which this allele variant might benefit power performance remains to be elucidated.
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References
Bray MS, Hagberg JM, Perusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C (2009) The human gene map for performance and health-related fitness phenotypes: the 2006–2007 update. Med Sci Sports Exerc 41:35–73
Cooke JP, Rossitch E Jr, Andon NA, Loscalzo J, Dzau VJ (1991) Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator. J Clin Invest 88:1663–1671
Garland TJ, Bernnet AF, Daniels CB (1990) Heritability of locomotor performance and its correlates in a natural population. Experientia 46:530–533
Hambrecht R, Fiehn E, Weigl C, Gielen S, Hamann C, Kaiser R, Yu J, Adams V, Niebauer J, Schuler G (1998) Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation 98:2709–2715
Hand BD, McCole SD, Brown MD, Park JJ, Ferrell RE, Huberty A, Douglass LW, Hagberg JM (2006) NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women. Int J Sports Med 27:951–958
Heydemann A, McNally E (2009) NO more muscle fatigue. J Clin Invest 119:448–450
Hickner RC, Fisher JS, Ehsani AA, Kohrt WM (1997) Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans. Am J Physiol 273:H405–H410
Higashi Y, Sasaki S, Sasaki N, Nakagawa K, Ueda T, Yoshimizu A, Kurisu S, Matsuura H, Kajiyama G, Oshima T (1999) Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension. Hypertension 33:591–597
Hyndman ME, Parsons HG, Verma S, Bridge PJ, Edworthy S, Jones C, Lonn E, Charbonneau F, Anderson TJ (2002) The T−786 → C mutation in endothelial nitric oxide synthase is associated with hypertension. Hypertension 39:919–922
Le Gouill E, Jimenez M, Binnert C, Jayet PY, Thalmann S, Nicod P, Scherrer U, Vollenweider P (2007) Endothelial nitric oxide synthase (eNOS) knockout mice have defective mitochondrial beta-oxidation. Diabetes 56:2690–2696
Loke KE, Laycock SK, Mital S, Wolin MS, Bernstein R, Oz M, Addonizio L, Kaley G, Hintze TH (1999a) Nitric oxide modulates mitochondrial respiration in failing human heart. Circulation 100:1291–1297
Loke KE, McConnell PI, Tuzman JM, Shesely EG, Smith CJ, Stackpole CJ, Thompson CI, Kaley G, Wolin MS, Hintze TH (1999b) Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption. Circ Res 84:840–845
Long JH, Lira VA, Soltow QA, Betters JL, Sellman JE, Criswell DS (2006) Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production. J Muscle Res Cell Motil 27:577–584
McConell GK, Kingwell BA (2006) Does nitric oxide regulate skeletal muscle glucose uptake during exercise? Exerc Sport Sci Rev 34:36–41
McNamara DM, Tam SW, Sabolinski ML, Tobelmann P, Janosko K, Venkitachalam L, Ofili E, Yancy C, Feldman AM, Ghali JK, Taylor AL, Cohn JN, Worcel M (2009) Endothelial nitric oxide synthase (NOS3) polymorphisms in African Americans with heart failure: results from the A-HeFT trial. J Card Fail 15:191–198
Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142
Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, Motoyama T, Saito Y, Ogawa Y, Miyamoto Y, Nakao K (1999) T−786 → C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 99:2864–2870
Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Ogawa H, Kugiyama K, Mizuno Y, Harada E, Nakamura S, Ito T, Saito Y, Miyamoto Y, Ogawa Y, Nakao K (2000) T(−786) → C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis. Am J Cardiol 86:628–634
Otani H (2009) The role of nitric oxide in myocardial repair and remodeling. Antioxid Redox Signal [Epub ahead of print]
Quyyumi AA, Dakak N, Andrews NP, Gilligan DM, Panza JA, Cannon RO 3rd (1995) Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 92:320–326
Rankinen T, Rice T, Perusse L, Chagnon YC, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C (2000) NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study. Hypertension 36:885–889
Robinson LJ, Weremowicz S, Morton CC, Michel T (1994) Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics 19:350–357
Ruiz JR, Gomez-Gallego F, Santiago C, Gonzalez-Freire M, Verde Z, Foster C, Lucia A (2009) Is there an optimum endurance polygenic profile? J Physiol 587:1527–1534
Salanova M, Schiffl G, Puttmann B, Schoser BG, Blottner D (2008) Molecular biomarkers monitoring human skeletal muscle fibres and microvasculature following long-term bed rest with and without countermeasures. J Anat 212:306–318
Santiago C, Ruiz JR, Muniesa CA, González-Freire M, Gómez-Gallego F, Lucia A (2009) Does the polygenic profile determine the potential for becoming a world-class athlete? Insights from the sport of rowing. Scand J Med Sci Sports [Epub ahead of print]
Saunders CJ, Xenophontos SL, Cariolou MA, Anastassiades LC, Noakes TD, Collins M (2006) The bradykinin beta 2 receptor (BDKRB2) and endothelial nitric oxide synthase 3 (NOS3) genes and endurance performance during Ironman Triathlons. Hum Mol Genet 15:979–987
Sellman JE, DeRuisseau KC, Betters JL, Lira VA, Soltow QA, Selsby JT, Criswell DS (2006) In vivo inhibition of nitric oxide synthase impairs upregulation of contractile protein mRNA in overloaded plantaris muscle. J Appl Physiol 100:258–265
Smith LW, Smith JD, Criswell DS (2002) Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload. J Appl Physiol 92:2005–2011
Tejedor D, Castillo S, Mozas P, Jimenez E, Lopez M, Tejedor MT, Artieda M, Alonso R, Mata P, Simon L, Martinez A, Pocovi M (2005) Reliable low-density DNA array based on allele-specific probes for detection of 118 mutations causing familial hypercholesterolemia. Clin Chem 51:1137–1144
Van Damme R, Wilson RS, Vanhooydonck B, Aerts P (2002) Performance constraints in decathletes. Nature 415:755–756
Wagner PD (2000) New ideas on limitations to VO2max. Exerc Sport Sci Rev 28:10–14
Wang XL, Sim AS, Wang MX, Murrell GA, Trudinger B, Wang J (2000) Genotype dependent and cigarette specific effects on endothelial nitric oxide synthase gene expression and enzyme activity. FEBS Lett 471:45–50
Wilkerson DP, Campbell IT, Jones AM (2004) Influence of nitric oxide synthase inhibition on pulmonary O2 uptake kinetics during supra-maximal exercise in humans. J Physiol 561:623–635
Wolfarth B, Rankinen T, Muhlbauer S, Ducke M, Rauramaa R, Boulay MR, Perusse L, Bouchard C (2008) Endothelial nitric oxide synthase gene polymorphism and elite endurance athlete status: the Genathlete study. Scand J Med Sci Sports 18:485–490
Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K (2003) ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 73:627–631
Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Sumida H, Sugiyama S, Kugiyama K, Ogawa H, Ogawa Y, Saito Y, Miyamoto Y, Nakao K (1998) A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Hum Genet 103:65–69
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This study was funded by funded by Progenika Biopharma and Sabiobbi S.L. (Spain), and partially supported by Consejo Superior de Deportes (CSD, ref # UPR10/08), Fondo de Investigaciones Sanitarias (FIS, ref. # PI061183), Spanish Ministry of Education (EX-2007-1124) and Swedish Council for Working Life and Social Research (FAS).
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Félix Gómez-Gallego and Jonatan R. Ruiz contributed equally to this work.
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Gómez-Gallego, F., Ruiz, J.R., Buxens, A. et al. The −786 T/C polymorphism of the NOS3 gene is associated with elite performance in power sports. Eur J Appl Physiol 107, 565–569 (2009). https://doi.org/10.1007/s00421-009-1166-7
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DOI: https://doi.org/10.1007/s00421-009-1166-7