Top

Published in:

01-11-2010 | Original Article

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

Authors: Zi-Hong He, Yang Hu, Yan-Chun Li, Da-Peng Bao, Jonatan R. Ruiz, Alejandro Lucia

Published in: European Journal of Applied Physiology | Issue 4/2010

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.

Available only for authorised users

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 94:915–922PubMed

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 21:566–572CrossRefPubMed

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

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 99:4586–4591CrossRefPubMed

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 12:1055–1061CrossRefPubMed

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 33:450–460CrossRefPubMed

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

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

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

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 21:116–124CrossRefPubMed

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 33:6000–6010CrossRefPubMed

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 93:215–228CrossRefPubMed

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 25:6649–6659CrossRefPubMed

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

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

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 102:2269–2275PubMed

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 412:139–142CrossRefPubMed

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 316:1331–1336CrossRefPubMed

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

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

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 25:488–494PubMed

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 272:2684–2695CrossRefPubMed

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 150:845–851CrossRefPubMed

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 19:867–873CrossRefPubMed

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

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 83:61–71CrossRefPubMed

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

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

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 111:352–357CrossRefPubMed

Title: Polymorphisms in the calcineurin genes are associated with the training responsiveness of cardiac phenotypes in Chinese young adults
Authors: Zi-Hong He
Yang Hu
Yan-Chun Li
Da-Peng Bao
Jonatan R. Ruiz
Alejandro Lucia
Publication date: 01-11-2010
Publisher: Springer-Verlag
Published in: European Journal of Applied Physiology / Issue 4/2010
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-010-1558-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2010

Plasma nesfatin-1 and glucoregulatory hormone responses to two different anaerobic exercise sessions

Cell-free plasma DNA and purine nucleotide degradation markers following weightlifting exercise

Exhaustive exercise reduces TNF-α and IFN-α production in response to R-848 via toll-like receptor 7 in mice

The degree of p70S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume

Combined cycle and run performance is maximised when the cycle is completed at the highest sustainable intensity

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people