Skip to main content
SpringerLink
Log in

Polymorphisms in the calcineurin genes are associated with the training responsiveness of cardiac phenotypes in Chinese young adults

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

Abstract

We studied the association of 55 polymorphisms in the PPP3CA, PPP3CB, PPP3CC, PPP3R1 and PPP3R2 genes with both (1) the pre-training levels and (2) responsiveness to endurance training (18 weeks), of echocardiographic variables. The latter were measured both before and after the training program at each of the following time points: before (rest), during and after cycle-ergometry exercise. Subjects were healthy young Chinese men of Han origin [n = 102; mean (SD) age: 19 ± 1 years]. To assess genotype:phenotype associations at pre-training, we used a one-factor (genotype) ANOVA for each polymorphism. To assess the association between each polymorphism and the training responsiveness of cardiac phenotypes, we used a two-factor (genotype x training) ANOVA with repeated measures. All multiple comparisons were corrected for mass significance. For genotype:phenotype associations at pre-training, we only found a significant association between the rs3763679 polymorphism (PPP3CB) and resting heart rate. As for genotype associations with trainability of cardiac phenotypes, we found the following significant associations (i.e. significant genotype × training interaction effect): (1) rs1879793, rs1075534, rs7430, rs2461483 and rs10108011 (PPP3CC) and cardiac output/stroke volume after exercise; and (2) rs1407877 (PPP3R2) and ejection fraction at 50 W. The findings suggest that polymorphisms in the calcineurin genes might be among the numerous potential genetic variant candidates that can help explaining human variations in the pre-training levels or trainability of cardiac phenotype traits.

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

References

  • Akhmetov II, Linde EV, Shikhova IuV, Popov DV, Missina SS, Vinogradoba OL, Rogozkin VA (2008) The influence of calcineurin gene polymorphism on morphofunctional characteristics of cardiovascular system of athletes. Ross Fiziol Zh Im I M Sechenova 94:915–922

    CAS  PubMed  Google Scholar 

  • An P, Rice T, Gagnon J, Leon AS, Skinner JS, Bouchard C, Rao DC, Wilmore JH (2000) Familial aggregation of stroke volume and cardiac output during submaximal exercise: the HERITAGE Family Study. Int J Sports Med 21:566–572

    Article  CAS  PubMed  Google Scholar 

  • Bassil N, Alkaade S, Morley JE (2009) The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag 5:427–448

    CAS  PubMed  Google Scholar 

  • Bueno OF, Wilkins BJ, Tymitz KM, Glascock BJ, Kimball TF, Lorenz JN, Molkentin JD (2002) Impaired cardiac hypertrophic response in Calcineurin Abeta -deficient mice. Proc Natl Acad Sci USA 99:4586–4591

    Article  CAS  PubMed  Google Scholar 

  • Deng L, Huang B, Qin D, Ganguly K, El-Sherif N (2001) Calcineurin inhibition ameliorates structural, contractile, and electrophysiologic consequences of postinfarction remodeling. J Cardiovasc Electrophysiol 12:1055–1061

    Article  CAS  PubMed  Google Scholar 

  • He Z, Hu Y, Feng L, Lu Y, Bao D, Xi Y, Wen L, Lucia A (2008) Association between HMOX-1 genotype and cardiac function during exercise. Appl Physiol Nutr Metab 33:450–460

    Article  CAS  PubMed  Google Scholar 

  • He ZH, Hu Y, Wang HY, Li YC, Lu YL, Zhang L, Bao BP, Ruiz JR, Lucia A (2010) Are calcineurin genes associated with endurance phenotype traits? Eur J Appl Physiol 109:359–369

    Google Scholar 

  • Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Statist 6:65–70

    Google Scholar 

  • Knight JC (2005) Regulatory polymorphisms underlying complex disease traits. J Mol Med 83:97–109

    Article  CAS  PubMed  Google Scholar 

  • Kristal-Boneh E, Silber H, Harari G, Froom P (2000) The association of resting heart rate with cardiovascular, cancer, all-cause mortality. Eight year follow-up of 3527 male Israeli employees (the CORDIS Study). Eur Heart J 21:116–124

    Article  CAS  PubMed  Google Scholar 

  • Mercado PA, Ayala YM, Romano M, Buratti E, Baralle FE (2005) Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. Nucleic Acids Res 33:6000–6010

    Article  CAS  PubMed  Google Scholar 

  • Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN (1998) A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93:215–228

    Article  CAS  PubMed  Google Scholar 

  • Oka T, Dai YS, Molkentin JD (2005) Regulation of calcineurin through transcriptional induction of the calcineurin A beta promoter in vitro and in vivo. Mol Cell Biol 25:6649–6659

    Article  CAS  PubMed  Google Scholar 

  • Parsons SA, Wilkins BJ, Bueno OF, Molkentin JD (2003) Altered skeletal muscle phenotypes in calcineurin Aalpha and Abeta gene-targeted mice. Mol Cell Biol 23:4331–4343

    Article  CAS  PubMed  Google Scholar 

  • Powers SK, Lennon SL, Quindry J, Mehta JL (2002) Exercise and cardioprotection. Curr Opin Cardiol 17:495–502

    Article  PubMed  Google Scholar 

  • Sakata Y, Masuyama T, Yamamoto K, Nishikawa N, Yamamoto H, Kondo H, Ono K, Otsu K, Kuzuya T, Miwa T, Takeda H, Miyamoto E, Hori M (2000) Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats. Circulation 102:2269–2275

    CAS  PubMed  Google Scholar 

  • Sasabe T, Furukawa A, Matsusita S, Higuchi S, Ishiura S (2007) Association analysis of the dopamine receptor D2 (DRD2) SNP rs1076560 in alcoholic patients. Neurosci Lett 412:139–142

    Article  CAS  PubMed  Google Scholar 

  • Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Bostrom K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336

    Article  CAS  PubMed  Google Scholar 

  • Schulz RA, Yutzey KE (2004) Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development. Dev Biol 266:1–16

    Article  CAS  PubMed  Google Scholar 

  • Shaffer JP (1995) Multiple hypothesis testing. Ann Rev Psych 46:561–584

    Article  Google Scholar 

  • Shang L, Jiang X, Bao XH, Xue FB, Xu YY (2007) Body mass index of male youths aged 18–20 years of the Han nationality living in different regions of China. J Health Popul Nutr 25:488–494

    PubMed  Google Scholar 

  • Strom CC, Aplin M, Ploug T, Christoffersen TE, Langfort J, Viese M, Galbo H, Haunso S, Sheikh SP (2005) Expression profiling reveals differences in metabolic gene expression between exercise-induced cardiac effects and maladaptive cardiac hypertrophy. FEBS J 272:2684–2695

    Article  CAS  PubMed  Google Scholar 

  • Tang W, Arnett DK, Devereux RB, Panagiotou D, Province MA, Miller MB, de Simone G, Gu C, Ferrell RE (2005) Identification of a novel 5-base pair deletion in calcineurin B (PPP3R1) promoter region and its association with left ventricular hypertrophy. Am Heart J 150:845–851

    Article  CAS  PubMed  Google Scholar 

  • Tauchmanova L, Carrano R, Sabbatini M, De Rosa M, Orio F, Palomba S, Cascella T, Lombardi G, Federico S, Colao A (2004) Hypothalamic-pituitary-gonadal axis function after successful kidney transplantation in men and women. Hum Reprod 19:867–873

    Article  PubMed  Google Scholar 

  • Vega RB, Bassel-Duby R, Olson EN (2003) Control of cardiac growth and function by calcineurin signaling. J Biol Chem 278:36981–36984

    Article  CAS  PubMed  Google Scholar 

  • Wagner N, Jehl-Pietri C, Lopez P, Murdaca J, Giordano C, Schwartz C, Gounon P, Hatem SN, Grimaldi P, Wagner KD (2009) Peroxisome proliferator-activated receptor beta stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin. Cardiovasc Res 83:61–71

    Article  CAS  PubMed  Google Scholar 

  • Wilkins BJ, Molkentin JD (2002) Calcineurin and cardiac hypertrophy: where have we been? Where are we going? J Physiol 541:1–8

    Article  CAS  PubMed  Google Scholar 

  • Wilkins BJ, Molkentin JD (2004) Calcium-calcineurin signaling in the regulation of cardiac hypertrophy. Biochem Biophys Res Commun 322:1178–1191

    Article  CAS  PubMed  Google Scholar 

  • Yosefy C, Jafari J, Klainman E, Brodkin B, Handschumacher MD, Vaturi M (2006) The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test. Int J Cardiol 111:352–357

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by grants from China Institute of Sport Science, and part of grants from Ministry of Science and Technology of the People’s Republic of China (Grant code: 2003BA904B04).

Author information

Authors and Affiliations

  1. Biology Center, China Institute of Sport Science, Beijing, China

    Zi-Hong He

  2. Science and Research Center, Beijing Sports University, Beijing, 100084, China

    Yang Hu, Yan-Chun Li & Da-Peng Bao

  3. Unit for Preventive Nutrition, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden

    Jonatan R. Ruiz

  4. Universidad Europea de Madrid, Madrid, Spain

    Alejandro Lucia

Authors
  1. Zi-Hong He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan-Chun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Da-Peng Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonatan R. Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alejandro Lucia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yang Hu.

Additional information

Communicated by Keith George.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, ZH., Hu, Y., Li, YC. et al. Polymorphisms in the calcineurin genes are associated with the training responsiveness of cardiac phenotypes in Chinese young adults. Eur J Appl Physiol 110, 761–767 (2010). https://doi.org/10.1007/s00421-010-1558-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-010-1558-8

Keywords

Search

Navigation