Download PDF
Int J Sports Med 2016; 37(05): 411-417
DOI: 10.1055/s-0035-1564257
Genetics & Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

CNTFR Genotype and Sprint/power Performance: Case-control Association and Functional Studies

E. Miyamoto-Mikami
1   Department of Sports and Life Science, National Institute of Fitness and Sports in Kanoya, Kanoya, Kagoshima Japan
,
Y. Fujita
2   Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
,
H. Murakami
3   Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan
,
M. Ito
2   Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
,
M. Miyachi
3   Department of Health Promotion and Exercise, National Institute of Health and Nutrition, Tokyo, Japan
,
T. Kawahara
4   General Director Research Departments, Japan Institute of Sports Sciences, Tokyo, Japan
,
N. Fuku
5   Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan
› Author Affiliations
Further Information

Publication History



accepted after revision 14 September 2015

Publication Date:
02 February 2016 (online)

Also available at
    Permissions and Reprints

Abstract

The aim of this study was to investigate whether rs41274853 in the 3′-untranslated region of the ciliary neurotrophic factor receptor gene (CNTFR) is associated with elite sprint/power athletic status and assess its functional significance. A total of 211 Japanese sprint/power track and field athletes (62 international, 72 national, and 77 regional athletes) and 814 Japanese controls were genotyped at rs41274853. Luciferase reporter assay was conducted to investigate whether this C-to-T polymorphism affects binding of microRNA miR-675-5p to this region. The TT genotype was significantly more frequent among international sprint/power athletes (19.4%) than in the controls after Bonferroni correction (7.9%, P=0.036, OR=2.81 [95% CI: 1.43–5.55]). Furthermore, in non-athletic young/middle-aged men (n=132), TT genotype carriers exhibited significantly greater leg extension power (26.6±5.4 vs. 24.0±5.4 W/kg BW, P=0.019) and vertical jump performance (50.1±6.9 vs. 47.9±7.5 cm, P=0.047) than the CC+CT genotype carriers. Reporter assays revealed that the miR-675-5p binds to this polymorphic region within the CNTFR mRNA, irrespective of the rs41274853 allele present. Although the functional significance of the rs41274853 polymorphism remains unclear, the CNTFR is one of the candidate genes contributing to sprint/power performance.

Key words

ciliary neurotrophic factor receptor - elite sprint/power athletes - single nucleotide polymorphism
 

  • References

  • 1 Ahmetov II, Fedotovskaya ON. Current Progress in Sports Genomics. Adv Clin Chem 2015; 70: 247-314
    PubMedGoogle Scholar
  • 2 Arking DE, Fallin DM, Fried LP, Li T, Beamer BA, Xue QL, Chakravarti A, Walston J. Variation in the ciliary neurotrophic factor gene and muscle strength in older Caucasian women. J Am Geriat Soc 2006; 54: 823-826
    CrossrefPubMedGoogle Scholar
  • 3 Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA 2007; 13: 313-316
    CrossrefPubMedGoogle Scholar
  • 4 Carmelli D, Reed T. Stability and change in genetic and environmental influences on hand-grip strength in older male twins. J Appl Physiol 2000; 89: 1879-1883
    PubMedGoogle Scholar
  • 5 Davis S, Aldrich TH, Valenzuela DM, Wong VV, Furth ME, Squinto SP, Yancopoulos GD. The receptor for ciliary neurotrophic factor. Science 1991; 253: 59-63
    CrossrefPubMedGoogle Scholar
  • 6 De Mars G, Windelinckx A, Beunen G, Delecluse C, Lefevre J, Thomis MA. Polymorphisms in the CNTF and CNTF receptor genes are associated with muscle strength in men and women. J Appl Physiol 2007; 102: 1824-1831
    CrossrefPubMedGoogle Scholar
  • 7 De Moor MH, Spector TD, Cherkas LF, Falchi M, Hottenga JJ, Boomsma DI, De Geus EJ. Genome-wide linkage scan for athlete status in 700 British female DZ twin pairs. Twin Res Hum Genet 2007; 10: 812-820
    CrossrefPubMedGoogle Scholar
  • 8 DeChiara TM, Vejsada R, Poueymirou WT, Acheson A, Suri C, Conover JC, Friedman B, McClain J, Pan L, Stahl N, Ip NY, Yancopoulos GD. Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. Cell 1995; 83: 313-322
    CrossrefPubMedGoogle Scholar
  • 9 Fraysse B, Guillet C, Huchet-Cadiou C, Camerino DC, Gascan H, Leoty C. Ciliary neurotrophic factor prevents unweighting-induced functional changes in rat soleus muscle. J Appl Physiol 2000; 88: 1623-1630
    PubMedGoogle Scholar
  • 10 Fuku N, Murakami H, Iemitsu M, Sanada K, Tanaka M, Miyachi M. Mitochondrial macrohaplogroup associated with muscle power in healthy adults. Int J Sports Med 2012; 33: 410-414
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Garatachea N, Lucia A. Genes and the ageing muscle: a review on genetic association studies. Age (Dordr) 2013; 35: 207-233
    CrossrefPubMedGoogle Scholar
  • 12 Guillet C, Auguste P, Mayo W, Kreher P, Gascan H. Ciliary neurotrophic factor is a regulator of muscular strength in aging. J Neurosci 1999; 19: 1257-1262
    PubMedGoogle Scholar
  • 13 Guillet C, Huchet-Cadiou C, Gascan H, Leoty C. Changes in CNTF receptor alpha expression in rat skeletal muscle during the recovery period after hindlimb suspension. Acta Physiol Scand 1998; 163: 273-278
    CrossrefPubMedGoogle Scholar
  • 14 Harriss DJ, Atkinson G. Ethical standards in sport and exercise science research: 2016 update. Int J Sports Med 2015; 36: 1121-1124
    Google Scholar
  • 15 Helgren ME, Squinto SP, Davis HL, Parry DJ, Boulton TG, Heck CS, Zhu Y, Yancopoulos GD, Lindsay RM, DiStefano PS. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell 1994; 76: 493-504
    CrossrefPubMedGoogle Scholar
  • 16 Ip NY, McClain J, Barrezueta NX, Aldrich TH, Pan L, Li Y, Wiegand SJ, Friedman B, Davis S, Yancopoulos GD. The alpha component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development. Neuron 1993; 10: 89-102
    CrossrefPubMedGoogle Scholar
  • 17 Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, Reik W. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nature Cell Biol 2012; 14: 659-665
    CrossrefPubMedGoogle Scholar
  • 18 Li X, Li D, Zhuang Y, Shi Q, Wei W, Ju X. Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL. Pediat Blood Cancer 2013; 60: 2060-2067
    PubMedGoogle Scholar
  • 19 Murakami H, Iemitsu M, Sanada K, Gando Y, Ohmori Y, Kawakami R, Sasaki S, Tabata I, Miyachi M. Associations among objectively measured physical activity, fasting plasma homocysteine concentration, and MTHFR C677T genotype. Eur J Appl Physiol 2011; 111: 2997-3005
    CrossrefPubMedGoogle Scholar
  • 20 Persi A, Maltese PE, Bertelli M, Cecchin S, Ciaghi M, Guarnieri MC, Agnello L, Maggioni MA, Merati G, Veicsteinas A. Polymorphisms of alpha-actinin-3 and ciliary neurotrophic factor in national-level Italian athletes. Panminerva medica 2013; 55: 217-224
    PubMedGoogle Scholar
  • 21 Pitsiladis Y, Wang G, Wolfarth B, Scott R, Fuku N, Mikami E, He Z, Fiuza-Luces C, Eynon N, Lucia A. Genomics of elite sporting performance: what little we know and necessary advances. Br J Sports Med 2013; 47: 550-555
    CrossrefPubMedGoogle Scholar
  • 22 Roth SM, Metter EJ, Lee MR, Hurley BF, Ferrell RE. C174T polymorphism in the CNTF receptor gene is associated with fat-free mass in men and women. J Appl Physiol 2003; 95: 1425-1430
    CrossrefPubMedGoogle Scholar
  • 23 Roth SM, Schrager MA, Ferrell RE, Riechman SE, Metter EJ, Lynch NA, Lindle RS, Hurley BF. CNTF genotype is associated with muscular strength and quality in humans across the adult age span. J Appl Physiol 2001; 90: 1205-1210
    PubMedGoogle Scholar
  • 24 Sato K, Yoshimura A, Kaneko T, Ukai T, Ozaki Y, Nakamura H, Li X, Matsumura H, Hara Y, Ogata Y. A single nucleotide polymorphism in 3′-untranslated region contributes to the regulation of Toll-like receptor 4 translation. J Biol Chem 2012; 287: 25163-25172
    CrossrefPubMedGoogle Scholar
  • 25 Sleeman MW, Anderson KD, Lambert PD, Yancopoulos GD, Wiegand SJ. The ciliary neurotrophic factor and its receptor, CNTFR alpha. Pharmaceut Acta Helv 2000; 74: 265-272
    PubMedGoogle Scholar
  • 26 Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics 2006; 22: 1928-1929
    CrossrefPubMedGoogle Scholar
  • 27 Vergara C, Ramirez B. CNTF a pleiotropic cytokine: emphasis on its myotrophic role. Brain Res Rev 2004; 47: 161-173
    CrossrefPubMedGoogle Scholar
  • 28 Walsh S, Kelsey BK, Angelopoulos TJ, Clarkson PM, Gordon PM, Moyna NM, Visich PS, Zoeller RF, Seip RL, Bilbie S, Thompson PD, Hoffman EP, Price TB, Devaney JM, Pescatello LS. CNTF 1357 G -> A polymorphism and the muscle strength response to resistance training. J A ppl Physiol 2009; 107: 1235-1240
    PubMedGoogle Scholar