PDF herunterladen
Int J Sports Med 2019; 40(05): 354-358
DOI: 10.1055/a-0824-5394
Genetics & Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

KCNA4 Gene Variant is Auxiliary in Endurance Running Performance Level

Keven Flecha-Velazquez
1   Department Physical Medicine, Rehabilitation & Sports Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
,
Thomas D. Fahey
2   Department Kinesiology, California State University - Chico, Chico, United States
,
Juan L. Martínez
3   Sinaloense Sports Institute, Sport Medicine and Applied Sciences Unit, Culiacan, Mexico
,
Juan R. Lopez-Taylor
4   Universidad de Guadalajara, Physical Activity and Applied Sport Sciences Institute, Guadalajara, Mexico
,
Miguel A. Rivera
1   Department Physical Medicine, Rehabilitation & Sports Medicine, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
27. Februar 2019 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

The present is an observational study following a genetic epidemiology model using a case-control design. We tested the hypothesis of an association between the prevalence of the genotypic and allelic frequencies distribution of the potassium voltage-gated channel of the shaker related subfamily member 4 gene (KCNA4) rs1323860 (C/T transition) and endurance performance level in Hispanic male marathon runners (MR). The subjects (n=1876) were adult Hispanic male MR. Fast-MR (cases; n=938) were finishers in the top 3rd percentile. Slow MR (controls; n=938) were finishers in the lowest 3rd percentile of their respective age. Genomic DNA was purified from a whole blood sample. Polymerase chain reaction was used to amplify a KCNA4 SNP which consists of a C/T (rs1323860) transition. The observed genotype frequencies, in both Cases and Controls, met Hardy-Weinberg equilibrium (X2, P≥0.05). Genotype and allele frequencies were statistically different (P<0.01) between cases and controls. Odds ratio revealed that the C allele was 1.33 times more likely prevalent in the cases than in the controls (95% CI; 1.17, 1.51; P<0.001). The magnitude of the statistical power for the present study was 0.86. In conclusion, the findings strongly suggest that KCNA4 gene rs1323860 (C/T transition) is auxiliary in the complex phenotype of endurance running performance level in Hispanic male marathon runners.

Key words

endurance athletes - case-control - genetic epidemiology
 

  • References

  • 1 Antzelevitch C, Burashnikov A. Overview of basic mechanisms of cardiac arrhythmia. Card Electrophysiol Clin 2011; 31: 23-45
    PubMedGoogle Scholar
  • 2 Botstein D, White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in man using restriction fragment length polymorphism. Am J Hum Genet 1980; 32: 314-331
    PubMedGoogle Scholar
  • 3 Bouchard C, Rankinen T, Chagnon YC, Rice T, Perusse L, Gagnon J, Borecki I, An P, Leon AS, Skinner JS, Wilmore JH, Province M, Rao DC. Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study. J Appl Physiol 2000; 88: 551-559
    CrossrefPubMedGoogle Scholar
  • 4 Bouchard C, Rice T, Perusse L, Gagnon J, Province MA, Leon AS, Rao DC, Skinner JS, Wilmore JH. Familial resemblance for VO2max in the sedentary state: the HERITAGE family study. Med Sci Sports Exerc 1998; 30: 252-258
    PubMedGoogle Scholar
  • 5 Bray MS, Hagberg JM, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes: The 2006–2007 update. Med Sci Sports Exerc 2006; 38: 1863-1888
    CrossrefPubMedGoogle Scholar
  • 6 Brooks GA, Fahey TD, Baldwin K. Exercise Physiology: Human Bioenergetics and Its Applications. 4th Edition ed. New York, NY: McGraw-Hill Publishing Company; 2005: 340-362
    Google Scholar
  • 7 Catterall WA. From ionic currents to molecular mechanisms. Neuron 2000; 26: 13-25
    CrossrefPubMedGoogle Scholar
  • 8 Core Team R. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, 2017. https://www.R-project.org/
    PubMed
  • 9 Coyle E. Integration of the physiological factors determining endurance performance ability. Exerc Sports Sci Rev 1995; 23: 25-64
    PubMedGoogle Scholar
  • 10 Gessler M, Grape A, Grzeschik K-H, Pongs O. The potassium channel gene HK1 maps to human chromosome 11p14.1, close to the FSHB gene. Hum Genet 1992; 90: 319-321
    PubMedGoogle Scholar
  • 11 González-Alonso J, Calbet JAL. Reductions in systematic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans. Circulation 2003; 107: 824-830
    CrossrefPubMedGoogle Scholar
  • 12 Grizel AV, Glukhov GS, Sokolova OS. Mechanisms of activation of voltage-gated potassium channels. Acta Naturae 2014; 6: 10-26
    PubMedGoogle Scholar
  • 13 Hall JE, Guyton AC. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia, PA: Saunders/Elsevier; 2011: 101-113
    Google Scholar
  • 14 Harriss DJ, Macsween A, Atkinson G. Standards for ethics in sport and exercise science research: 2018 update. Int J Sports Med 2017; 38: 1126-1131
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 15 Heath GW, Hagberg JM, Ehsani AA, Holloszy JO. A physiological comparison of young and older endurance athletes. J Appl Physiol 1981; 51: 634-640
    CrossrefPubMedGoogle Scholar
  • 16 Howarth FC, Jacobson M, Shafiullah M, Adeghate E. Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto–Kakizaki rat. Exp Physiol 2008; 93: 362-369
    CrossrefPubMedGoogle Scholar
  • 17 Li Y, Shiffman D, Oberbauer R. Analysis of single nucleotide polymorphisms in case–control studies. In: Mayer B. (ed.) Bioinformatics for Omics Data Methods in Molecular Biology (Methods and Protocols). NJ: Humana Press; 2011: 219-234
    Google Scholar
  • 18 Long SB, Campbell EB, MacKinnon R. Crystal structure of a mamalian voltage dependent shaker family K+channel. Science 2005; 309: 897-903
    CrossrefPubMedGoogle Scholar
  • 19 Martínez JL, Carrión A, Florián ME, Martín JA, López-Taylor JR, Fahey TD, Rivera MA. Aquaporin-1 gene DNA variation predicts performance in hispanic marathon runners. Medicina Sportiva 2009; 13: 251-255
    CrossrefPubMedGoogle Scholar
  • 20 Miyamoto-Mikami E, Zempo H, Fuku N, Kikuchi N, Miyachi M, Murakami H. Heritability estimates of endurance-related phenotypes: A systematic review and meta-analysis. Scand J Med Sci Sports 2018; 28: 834-845
    CrossrefPubMedGoogle Scholar
  • 21 Nerbonne JM, Kass RS. Molecular physiology of cardiac repolarization. Physiol Rev 2005; 85: 1205-1253
    CrossrefPubMedGoogle Scholar
  • 22 Noakes St TD, Clair GA, Lambert EV. From catastrophe to complexity: A novel model of integrative central neural regulation of effort and fatigue during exercise in humans: Summary and conclusions. Br J Sports Med 2005; 39: 120-124
    CrossrefPubMedGoogle Scholar
  • 23 Ott J. Analysis of Human Genetic Linkage. 3 ed. Baltimore, MD: John Hopkins University Press; 1999: 28-29
    Google Scholar
  • 24 Rivera MA, Dionne FT, Simoneau J-A, Perusse L, Chagnon M, Chagnon Y, Gagnon J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C. Muscle-specific creatine kinase gene polymorphism and VO2max in the HERITAGE Family Study. Med Sci Sports Exerc 1997; 29: 1311-1317
    CrossrefPubMedGoogle Scholar
  • 25 Rivera MA, Martinez JL, Carrion AA, Fahey TD. AQP-1 association with body fluid loss in 10-km runners. Int J Sports Med 2011; 32: 223-229
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 26 Salem KA, Adrian TE, Qureshi MA, Parekh K, Oz M, Howarth FC. Shortening and intracellular Ca2+in ventricular myocytes and expression of genes encoding cardiac muscle proteins in early onset type 2 diabetic Goto–Kakizaki rats. Exp Physiol 2012; 97: 1281-1291
    CrossrefPubMedGoogle Scholar
  • 27 Sarzynski MA, Loos RJF, Lucia A, Perusse L, Roth SM, Wolfarth B, Rankinen T, Bouchard C. Advances in Exercise, Fitness, and Performance Genomics in 2015. Med Sci Sports Exerc 2016; 48: 1906-1916
    CrossrefPubMedGoogle Scholar
  • 28 Saunders CJ, Posthumus M, O’connell K, September AV, Collins M. A variant within the AQP1 3'-untranslated region is associated with running performance, but not weight changes, during an Ironman Triathlon. J Sports Sci 2015; 33: 1342-1348
    CrossrefPubMedGoogle Scholar
  • 29 Snyders DJ. Structure and function of cardiac potassium channels. Cardiovasc Res 1999; 42: 377-390
    CrossrefPubMedGoogle Scholar
  • 30 Swart J, Lamberts RP, Lambert St MI, Clair Gibson A, Lambert EV, Skowno J, Noakes TD. Exercising with reserve: Evidence that the CNS regulates prolonged exercise performance. Br J Sports Med 2008; 43: 782-788
    PubMedGoogle Scholar
  • 31 Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, Glover DM. Molecular cloning and characterization of two voltage-gated K+channel cDNAs from human ventricle. FASEB J 1991; 5: 331-337
    CrossrefPubMedGoogle Scholar
  • 32 Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol 2001; 37: 153-156
    CrossrefPubMedGoogle Scholar
  • 33 Whitehead Institute for Genome Research Variations in genomic region of KCNA4. [cited 2018 may 8]; Retrieved from https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1323860 In 2018
    PubMed
  • 34 Wissmann R, Bildl W, Oliver D, Beyermann M, Kalbitzer H-R, Bentrop D, Fakler B. Solution structure and function of the “tandem inactivation domain” of the neuronal a-type potassium channel Kv1.4. J Biol Chem 2003; 278: 16142-16150
    CrossrefPubMedGoogle Scholar