Top

Published in:

01-03-2020 | Review

ACTN3 R/X gene polymorphism across ethnicity: a brief review of performance gene

Authors: Hazwani Ahmad Yusof, Wan Nor Syahirah Nasaruddin, Ahmad Munir Che Muhamed

Published in: Sport Sciences for Health | Issue 1/2020

Abstract

Alpha-actinin-3 (ACTN3) gene is one of the most extensively investigated genes associated with human physical performance. The ACTN3 gene via ACTN3 R/X gene polymorphism codes the ACTN3 protein proteins that are localized at the boundaries of sarcomeres in the contractile apparatus of muscle Z disk. The ACTN3 R allele codes for functioning ACTN3 gene that results in the production of ACTN3 protein, while incomplete sequence in the ACTN3 X allele, preventing the production of that protein. Given these different physiological functions, possession of the ACTN3 R and X alleles may grant beneficial effects of strength/power and endurance activities, respectively. It has remained uncertain if human physical performance is indeed influenced by ACTN3 R/X gene polymorphisms as some studies have failed to demonstrate positive findings. It has been speculated that the inconsistencies observed in the present findings may be due to ethnicity differences as the distributions of ACTN3 R/X gene polymorphism has been reported to vary across ethnic groups in general populations worldwide. Therefore, the aim of this review is to provide a brief review of ACTN3 R/X gene polymorphism, including distribution pattern across ethnicity and its association on human physical performance based on population studies. Therefore, this review could serve as the basis for future research towards a better comprehension of the involvement of the ACTN3 R/X gene polymorphism on human physical performance across different ethnic groups.

Baker J, Davids K (2006) Genetic and environmental constraints on variability in sport performance. In: Davids K, Bennett S, Newell KM (eds) Movement system variability. Human Kinetics, USA, pp 109–132

Silventoinen K, Magnusson PK, Tynelius P, Kaprio J, Rasmussen F (2008) Heritability of body size and muscle strength in young adulthood: a study of one million Swedish men. Genet Epidemiol 32(4):341–349PubMed

Chatterjee S, Das N (1995) Physical and motor fitness in twins. Jpn J Physiol 45(3):519–534PubMed

Calvo M, Rodas G, Vallejo M, Estruch A, Arcas A, Javierre C, Viscor G, Ventura JL (2002) Heritability of explosive power and anaerobic capacity in humans. Euro J Appl Physiol 86(3):218–225

Maridaki M (2006) Heritability of neuromuscular performance and anaerobic power in preadolescent and adolescent girls. J Sports Med Phys Fit 46(4):540–547

Alonso L, Souza E, Oliveira M, do Nascimento L, Dantas P (2014) Heritability of aerobic power of individuals in northeast Brazil. Biol Sport 31(4):267–270PubMedPubMedCentral

Bouchard C, Leon AS, Rao DC, Skinner JS, Wilmore JH, Gagnon J (1995) The HERITAGE family study. Aims, design, and measurement protocol. Med Sci Sports Exerc 27(5):721–729PubMed

Rankinen T, Pérusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C (2001) The human gene map for performance and health-related fitness phenotypes. Med Sci Sports Exerc 33(6):855–867PubMed

Rankinen T, Pérusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C (2002) The human gene map for performance and health-related fitness phenotypes: the 2001 update. Med Sci Sports Exerc 34(8):1219–1233PubMed

10.

Rankinen T, Pérusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C (2004) The human gene map for performance and health-related fitness phenotypes: the 2003 update. Med Sci Sports Exerc 36(9):1451–1469PubMed

11.

Wolfarth B, Bray MS, Hagberg JM, Pérusse L, Rauramaa R, Rivera MA, Roth SM, Rankinen T, Bouchard C (2005) The human gene map for performance and health-related fitness phenotypes: the 2004 update. Med Sci Sports Exerc 37(6):881–903PubMed

12.

Rankinen T, Bray MS, Hagberg JM, Pérusse L, Roth SM, Wolfarth B, Bouchard C (2006) The human gene map for performance and health-related fitness phenotypes. Med Sci Sports Exerc 38(11):1863–1888PubMed

13.

Bray MS, Hagberg JM, Pérusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C (2009) The human gene map for performance and health-related fitness phenotypes. Med Sci Sports Exerc 41(1):35–73PubMed

14.

Rankinen T, Roth SM, Bray MS, Loos R, Pérusse L, Wolfarth B, Hagberg JM, Bouchard C (2010) Advances in exercise, fitness, and performance genomics. Med Sci Sports Exerc 42(5):835–846PubMed

15.

Hagberg JM, Rankinen T, Loos RJ, Perusse L, Roth SM, Wolfarth B, Bouchard C (2011) Advances in exercise, fitness, and performance genomics in 2010. Med Sci Sports Exerc 43(5):743–752PubMedPubMedCentral

16.

Roth SM, Rankinen T, Hagberg JM, Loos RJ, Perusse L, Sarzynski MA, Wolfarth B, Bouchard C (2012) Advances in exercise, fitness, and performance genomics in 2011. Med Sci Sports Exerc 44(5):809–817PubMedPubMedCentral

17.

Pérusse L, Rankinen T, Hagberg JM, Loos RJF, Roth SM, Sarzynski MA, Wolfarth B, Bouchard C (2013) Advances in exercise, fitness, and performance genomics in 2012. Med Sci Sports Exerc 45(5):824–831PubMedPubMedCentral

18.

Loos RJ, Hagberg JM, Pérusse L, Roth SM, Sarzynski MA, Wolfarth B, Rankinen T, Bouchard C (2015) Advances in exercise, fitness, and performance genomics in 2014. Med Sci Sports Exerc 47(6):1105–1112PubMedPubMedCentral

19.

Ma F, Yang Y, Li X, Zhou F, Gao C, Li M, Gao L (2013) The association of sport performance with ACE and ACTN3 genetic polymorphisms: a systematic review and meta-analysis. PLoS One 8(1):e54685PubMedPubMedCentral

20.

North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH (1999) A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nat Genet 21(4):353–354PubMed

21.

MacArthur DG, Seto JT, Raftery JM, Quinlan KG, Huttley GA, Hook JW, Lemckert FA, Kee AJ, Edwards MR, Berman Y, Hardeman EC, Gunning PW, Easteal S, Yang N, North KN (2007) Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet 39(10):1261–1265PubMed

22.

North K (2008) Why is alpha-actinin-3 deficiency so common in the general population? The evolution of athletic performance. Twin Res Hum Genet 11(4):384–394PubMed

23.

Yang N, MacArthur DG, Wolde B, Onywera VO, Boit MK, Lau SY, Wilson RH, Scott RA, Pitsiladis YP, North K (2007) The ACTN3 R577X polymorphism in East and West African athletes. Med Sci Sports Exerc 39(11):1985–1988PubMed

24.

Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K (2001) Differential expression of the actin-binding proteins, alpha-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. Hum Mol Genet 10(13):1335–1346PubMed

25.

Scott RA, Irving R, Irwin L, Morrison E, Charlton V, Austin K, Tladi D, Deason M, Headley SA, Kolkhorst FW, Yang N, North K, Pitsiladis YP (2010) ACTN3 and ACE genotypes in elite Jamaican and US sprinters. Med Sci Sports Exerc 42(1):107–112PubMed

26.

Druzhevskaya AM, Ahmetov II, Astratenkova IV, Rogozkin VA (2008) Association of the ACTN3 R577X polymorphism with power athlete status in Russians. Euro J Appl Physiol 103(6):631–634

27.

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(3):627–631PubMedPubMedCentral

28.

Fattahi Z, Najmabadi H (2012) Prevalence of ACTN3 (the athlete gene) R577X polymorphism in Iranian population. Iran Red Crescent Med J 14(10):617–622PubMedPubMedCentral

29.

Yusof HA, Zainuddin Z, Rooney K, Muhamed AMC (2017) Distributions of ACE I/D and ACTN3 R/X gene polymorphisms in multi-ethnic malaysian and australian populations. Int J Public Health Clin Sci 4(5):125–138

30.

Goel H, Mittal B (2007) ACTN3: athlete gene prevalence in North India. Curr Sci 92(1):84–86

31.

Comas D, Calafell F, Mateu E, Perez-Lezaun A, Bosch E, Martinez-Arias R, Clarimon J, Facchini F, Fiori G, Luiselli D, Pettener D, Bertranpetit J (1998) Trading genes along the silk road: mtDNA sequences and the origin of central Asian populations. Am J Hum Genet 63(6):1824–1838PubMedPubMedCentral

32.

Niemi A-K, Majamaa K (2005) Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet 13(8):965–969PubMed

33.

Eynon N, Durate JA, Oliveira J, Sagiv M, Yamin C, Meckel Y, Sagiv M, Goldhammer E (2009) ACTN3 R577X polymorphism and Israeli top-level athletes. Int J Sports Med 30(9):695–698PubMed

34.

Roth SM, Walsh S, Liu D, Metter EJ, Ferrucci L, Hurley BF (2008) The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Eur J Hum Genet 16(3):391–394PubMed

35.

Massidda M, Vona G, Calò CM (2009) Association between the ACTN3 R577X polymorphism and artistic gymnastic performance in Italy. Genet Test Mol Biomarkers 13(3):377–380PubMed

36.

Kothari ST, Chheda Pratiksha, Chawla S, Chatterjee L, Chaudhry SK, Das BR (2011) ACTN3 R577X polymorphism in Asian Indian athletes. Int J Hum Genet 11(3):149–153

37.

Cieszczyk P, Eider J, Ostanek M, Arczewska A, Leonska-Duniec A, Sawczyn S, Ficek K, Krupecki K (2011) Association of the ACTN3 R577X polymorphism in polish power-orientated athletes. J Hum Kinet 28:55–61PubMedPubMedCentral

38.

Clarkson PM, Devaney JM, Gordish-Dressman H, Thompson PD, Hubal MJ, Urso M, Price TB, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Hoffman EP (2005) ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol 99(1):154–163PubMed

39.

Moran CN, Yang N, Bailey MES, Tsiokanos A, Jamurtas A, MacArthur DG, North K, Pitsiladis YP, Wilson RH (2006) Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks. Eur J Hum Genet 15(1):88–93PubMed

40.

Vincent B, De Bock K, Ramaekers M, Van den Eede E, Van Leemputte M, Hespel P, Thomis MA (2007) ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics 32(1):58–63PubMed

41.

Norman B, Esbjörnsson M, Rundqvist H, Osterlund T, von Walden F, Tesch PA (2009) Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes. J Appl Physiol 106(3):959–965PubMed

42.

Shang X, Zhang F, Zhang L, Huang C (2012) ACTN3 R577X polymorphism and performance phenotypes in young Chinese male soldiers. J Sports Sci 30(3):255–260PubMed

43.

Erskine RM, Williams AG, Jones DA, Stewart CE, Degens H (2014) The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training. Scand J Med Sci Sports 24:642–648PubMed

44.

Clarkson PM, Hoffman EP, Zambraski E, Gordish-Dressman H, Kearns A, Hubal M, Harmon B, Devaney JM (2005) ACTN3 and MLCK genotype associations with exertional muscle damage. J Appl Physiol 99(2):564–569PubMed

45.

Delmonico MJ, Kostek MC, Doldo NA, Hand BD, Walsh S, Conway JM, Carignan CR, Roth SM, Hurley BF (2007) Alpha-actinin-3 (ACTN3) R577X polymorphism influences knee extensor peak power response to strength training in older men and women. J Gerontol A Biol Sci Med Sci 62(2):206–212PubMed

46.

Ichinoseki-Sekine N, Naito H, Harima H, Nakagawa K, Katamoto S (2010) Effects of home-based resistance training among elderly Japanese women with diŠerent ACTN3 (R577X) genotypes. Juntendo Health Sports Sci 1(4):486–493

47.

Gentil P, Pereira RW, Leite TKM, Bottaro M (2011) ACTN3 577X polymorphism and neuromuscular response to resistance training. J Sports Sci Med 10:393–399PubMedPubMedCentral

48.

Lucia A, Gómez-Gallego F, Santiago C, Bandrés F, Earnest C, Rabadán M, Alonso J, Hoyos J, Córdova A, Villa G, Foster C (2006) ACTN3 genotype in professional endurance cyclists. Int J Sports Med 27(11):880–884PubMed

49.

Santiago C, Rodriguez-Romo G, Gomez-Gallego F, Gonzalez-Freire M, Yvert T, Verde Z, Naclerio F, Altmae S, Esteve-Lanao J, Ruiz JR, Lucia A (2010) Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young, non-athletic adults? Scand J Med Sci Sports 20(5):771–778PubMed

50.

McCauley T, Mastana SS, Folland JP (2010) ACE I/D and ACTN3 R/X polymorphisms and muscle function and muscularity of older Caucasian men. Euro J Appl Physiol 109(2):269–277

51.

Djarova T, Watson G, Basson A, Grace J, Cloete J, Ramakoaba A (2011) ACTN3 and TNF gene polymorphism association with C-reactive protein, uric acid, lactate and physical characteristics in young African cricket players. Afr J Biochem Res 5(1):22–27

52.

Gineviciene V, Pranculis A, Jakaitiene A, Milasius K, Kucinskas V (2011) Genetic variation of the human ACE and ACTN3 genes and their association with functional muscle properties in Lithuanian elite athletes. Medicina (Kaunas) 47(5):284–290

53.

Wang G, Mikami E, Chiu LL, Deason M, Fuku N, Miyachi H, Kaneoka K, Murakami H, Tanaka M, Hsieh LL, Caporossi D, Pigozzi F, Hilley A, Lee R, Galloway SD, Gulbin J, Rogozkin VA, Ahmetov I, Yang N, North KN, Ploutarhos S, Montgomery HE, Bailey ME, Pitsiladis YP (2013) Association analysis of ACE and ACTN3 in elite Caucasian and East Asian swimmers. Med Sci Sports Exerc 45(5):892–900PubMed

54.

Ahmetov II, Gavrilov DN, Astratenkova IV, Druzhevskaya AM, Malinin AV, Romanova EE, Rogozkin VA (2013) The association of ACE, ACTN3 and PPARA gene variants with strength phenotypes in middle school-age children. J Physiol Sci 63(1):79–85PubMed

55.

Yusof HA, Singh R, Zainuddin Z, Rooney K, Muhamed AMC (2016) Alpha-Actinin-3 (ACTN3) R/X gene polymorphism and physical performance of multi-ethnic malaysian population. Int J Appl Exerc Physiol 5(1):18–30

56.

MacArthur DG, Seto JT, Chan S, Quinlan KG, Raftery JM, Turner N, Nicholson MD, Kee AJ, Hardeman EC, Gunning PW, Cooney GJ, Head SI, Yang N, North KN (2008) An Actn3 knockout mouse provides mechanistic insights into the association between alpha-actinin-3 deficiency and human athletic performance. Hum Mol Genet 17(8):1076–1086PubMed

57.

Allen DG, Lamb GD, Westerblad H (2008) Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 88(1):287–332PubMed

58.

Shang X, Huang C, Chang Q, Zhang L, Huang T (2010) Association between the ACTN3 R577X polymorphism and female endurance athletes in China. Int J Sports Med 31(12):913–916PubMed

59.

Lucia A, Gomez-Gallego F, Santiago C, Perez M, Mate-Munoz JL, Chamorro-Vina C, Nogales-Gadea G, Foster C, Rubio JC, Andreu AL, Martin MA, Arenas J (2007) The 577X allele of the ACTN3 gene is associated with improved exercise capacity in women with McArdle’s disease. Neuromuscul Disord 17(8):603–610PubMed

60.

San Juan AF, Gomez-Gallego F, Canete S, Santiago C, Perez M, Lucia A (2006) Does complete deficiency of muscle a actinin 3 alter functional capacity in elderly women? A preliminary report. Br J Sports Med 40(1):e1PubMed

61.

Ahmetov II, Druzhevskaya AM, Astratenkova IV, Popov DV, Vinogradova OL, Rogozkin VA (2008) The ACTN3 R577X polymorphism in Russian endurance athletes. Br J Sports Med 44(9):649–652PubMed

62.

Gomez-Gallego F, Santiago C, Gonzalez-Freire M, Muniesa CA, Fernandez Del Valle M, Perez M, Foster C, Lucia A (2009) Endurance performance: genes or gene combinations? Int J Sports Med 30(1):66–72PubMed

63.

Döring FE, Onur S, Geisen U, Boulay MR, Pérusse L, Rankinen T, Rauramaa R, Wolfahrt B, Bouchard C (2010) ACTN3R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study. J Sports Sci 28(12):1355–1359PubMed

64.

Zilberman-Schapira G, Chen J, Gerstein M (2012) On sports and genes. Recent Pat DNA Gene Seq. 6:180–188PubMed

65.

Guilherme JPLF, Tritto ACC, North KN, Lancha Junior AH, Artioli GG (2014) Genetics and sport performance: current challenges and directions to the future. Rev Bras Educ Fís Esporte 28:177–193

66.

Massidda M, Corrias L, Scorcu M, Vona G, Calò MC (2012) ACTN-3 and ACE genotypes in elite male Italian athletes. Anthropol Rev 75(1):51–59

67.

Pimenta EM, Coelho DB, Cruz IR, Morandi RF, Veneroso CE, Azambuja Pussieldi G, Carvalho MRS, Silami-Garcia E, Paz Fernández JA (2011) The ACTN3 genotype in soccer players in response to acute eccentric training. Euro J Appl Physiol 112(4):1495–1503

68.

Mayne I (2006) Examination of the ACE and ACTN3 genes in UTC varsity athletes sedentary students. The University of Tennessee at Chattanooga

69.

Ahmetov II, Druzhevskaya AM, Lyubaeva EV, Popov DV, Vinogradova OL, Williams AG (2011) The dependence of preferred competitive racing distance on muscle fibre type composition and ACTN3 genotype in speed skaters. Exp Physiol. 96(12):1302–1310PubMed

Title: ACTN3 R/X gene polymorphism across ethnicity: a brief review of performance gene
Authors: Hazwani Ahmad Yusof
Wan Nor Syahirah Nasaruddin
Ahmad Munir Che Muhamed
Publication date: 01-03-2020
Publisher: Springer Milan
Published in: Sport Sciences for Health / Issue 1/2020
Print ISSN: 1824-7490
Electronic ISSN: 1825-1234
DOI: https://doi.org/10.1007/s11332-019-00584-8

2024 ASCO Annual Meeting

Springer Medicine

ACTN3 R/X gene polymorphism across ethnicity: a brief review of performance gene

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

A study of dividing the group by age of health-related fitness in Taiwan

Does silica–nylon mesh improves the biomechanical response of custom-made mouthguards?

Prolonged visual reaction time after strenuous endurance exercise: higher increment in male compared to female recreational runners

The 1-s interpolation of breath-by-breath O2 uptake data to determine kinetic parameters: the misleading procedure

Italian student-athletes only need a more effective daily schedule to support their dual career

Weight loss behaviors in Brazilian mixed martial arts athletes