ACTN3 R577X and ACE I/D Polymorphisms and Sports Performance: A Systematic Review
Abstract
Background: Sporting performance is a multifactorial phenomenon that is affected by many factors. Several polymorphisms have recently been associated with sports performance. ACE I/D and ACTN3 R577X gene polymorphisms are some of these. This study aimed to investigate the relationship between ACTN3 R577X and ACE I/D polymorphisms and sports performance together with the results of studies conducted in the literature.
Methods: The review included studies on the relationship between ACTN3 R577X and ACE I/D polymorphisms and sports performance from Feb 2014 to Feb 2024. The studies registered in PubMed, PubMed Central and Google Scholar search engines were scanned. The present review included 756 cases, 2,191 controls, and 178 individuals from the cross-sectional and longitudinal studies. The PRISMA checklist and flow diagram were used to include data in the review.
Results: The review started with 224 studies, and the number of studies was reduced by 9. Then, a risk analysis was performed to determine whether 9 articles had a risk of bias. In the risk analysis conducted using the ROBINS-I tool, 3 articles were moderate, 3 articles were serious, and 3 articles were critical. Additionally, in the review, significant differences were found in 5 of the 9 studies (P<0.05).
Conclusion: ACTN3 R577X and ACE I/D polymorphisms may be evaluated together with many parameters related to performance. To our knowledge, ACTN3 R577X and ACE I/D polymorphisms may be important regulators for sports performance.
1. Varillas-Delgado D, Coso J, Gutiérrez-Hellín J, et al (2022). Genetics and sports performance: the present and future in the identification of talent for sports based on DNA testing. Eur J Appl Phys-iol, 122(8):1811-1830.
2. Végh D, Reichwalderová K, Slaninová M, et al (2022). The effect of selected pol-ymorphisms of the ACTN3, ACE, HIF1A and PPARA genes on the imme-diate supercompensation training effect of elite Slovak endurance runners and football players. Genes (Basel), 13(9):1525.
3. Almeida KY, Cetolin T, Marrero AR, et al (2022). A pilot study on the prediction of non-contact muscle injuries based on ACTN3 R577X and ACE I/D polymor-phisms in professional soccer athletes. Genes (Basel), 13(11):2009.
4. Manning JT, Fink B (2020). Understanding COVID-19: A hypothesis regarding digit ratio (2D:4D), ACE I/D polymorphism, oxygen metabolism and national case fatality rates. Early Hum Dev, 151:10561.
5. Vostrikova A, Pechenkina V, Danilova M, et al (2022). Gene polymorphism and to-tal genetic score in martial arts athletes with different athletic qualifications. Genes (Basel), 13(9):1677.
6. Ortiz AM, Laguarta-Val S, Varillas-Delgado D (2021). Muscle work and its relation-ship with ACE and ACTN3 polymor-phisms are associated with the im-provement of explosive strength. Genes (Basel), 12(8):1177.
7. Maffulli N, Margiotti K, Longo UG, et al (2013). The genetics of sports injuries and athletic performance. Muscles Liga-ments Tendons J, 3(3):173-89.
8. Goleva-Fjellet S, Bjurholt AM, Kure EH, et al (2020). Distribution of allele frequen-cies for genes associated with physical activity and/or physical capacity in a homogenous Norwegian cohort- a cross-sectional study. BMC Genet, 21(1):8.
9. Kumagai H, Miller B, Kim SJ, et al (2023). Novel insights into mitochondrial DNA: Mitochondrial microproteins and mtDNA variants modulate athletic per-formance and age-related diseases. Genes (Basel), 14(2):286.
10. Tharabenjasin P, Pabalan N, Jarjanazi H (2019). Association of the ACTN3 R577X (rs1815739) polymorphism with elite power sports: A meta-analysis. PLoS One, 14(5):e0217390.
11. Baltazar-Martins G, Gutiérrez-Hellín J, Aguilar-Navarro M, et al (2020). Effect of ACTN3 genotype on sports perfor-mance, exercise-induced muscle dam-age, and injury epidemiology. Sports (Ba-sel), 8(7):99.
12. Appel M, Zentgraf K, Krüger K, et al (2021). Effects of genetic variation on endur-ance performance, muscle strength, and injury susceptibility in sports: A system-atic review. Front Physiol, 21:12:694411.
13. Edwards AWF, GH Hardy (2008). (1908) and Hardy-Weinberg equilibrium. Genet-ics, 179(3):1143-1150.
14. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting system-atic reviews. BMJ, 372:n71.
15. Higgins JPT, Thomas J, Chandler J, Cump-ston M, Li T, Page MJ, Welch VA edi-tors. Cochrane Handbook for Systemat-ic Reviews of Interventions version 6.5 (updated August 2024). Cochrane, 2024.
16. McGuinness LA, Higgins JPT (2021). Risk-of-bias VISualization (robvis): An R package and shiny web app for visualiz-ing risk-of-bias assessments. Res Synth Methods, 12(1):55-61.
17. Yang S, Lin W, Jia M, et al (2023). Associa-tion between ACE and ACTN3 genes polymorphisms and athletic perfor-mance in elite and sub-elite Chinese youth male football players. PeerJ, 11:e14893.
18. Wei Q (2021). The ACE and ACTN3 poly-morphisms in female soccer athletes. Genes Environ, 43(1):5.
19. Gineviciene V, Jakaitiene A, Aksenov MO, et al (2016). Association analysis of ACE, ACTN3 and PPARGC1A gene poly-morphisms in two cohorts of European strength and power athletes. Biol Sport,33(3):199-206.
20. Onori ME, Pasqualetti M, Moretti G, et al (2022). Genetics and sport injuries: New perspectives for athletic excellence in an Italian court of rugby union players. Genes, 13(6):995.
21. Pasqualetti M, Onori ME, Canu G, et al (2022). The relationship between ACE, ACTN3 and MCT1 genetic polymor-phisms and athletic performance in Elite rugby union players: A preliminary study. Genes (Basel), 13(6):969.
22. Kim JH, Jung ES, Kim CH, et al (2014). Ge-netic associations of body composition, flexibility and injury risk with ACE, ACTN3 and COL5A1 polymorphisms in Korean ballerinas. J Exerc Nutrition Bio-chem, 18 (2):205-14.
23. Grenda A, Leońska-Duniec A, Kaczmar-czyk M, et al (2014). Interaction between ACE I/D and ACTN3 R577X polymor-phisms in Polish competitive swimmers. J Hum Kinet, 42:127-36.
24. Bosnyák E, Trájer E, Udvardy A, et al (2015). ACE and ACTN3 genes poly-morphisms among female Hungarian athletes in the aspect of sport disci-plines. Acta Physiologica Hungarica, 102 (4):451-8.
25. Erskine RM, Williams AG, Jones DA, et al (2013). The individual and combined in-fluence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training. Scand J Med Sci Sports, 24(4):642-8.
26. Peña-Vázquez O, Castillo LE, González-Chávez SA, et al (2023). Prevalence of polymorphism and post-training expres-sion of ACTN3 (R/X) and ACE (I/D) genes in crossFit athletes. Int J Environ Res Public Health, 20(5):4404.
27. Romero-Blanco C, Artiga-González MJ, Gómez-Cabello A, et al (2023). Strength and endurance training in older women in relation to ACTN3 R577X and ACE I/D polymorphisms. Int J Environ Res Public Health, 20(5):4404.
28. Galeandro V, Notarnicola A, Bianco A, et al (2017). ACTN3/ACE genotypes and mitochondrial genome in professional soccer players’ performance. J Biol Regul Homeost Agents, 31(1):207-213.
29. Doggun M (2022). Strategic role of genetic testing in direction to sports brach. J Turk Sport Sci, 5(2):155-167.
30. Gasser B, Flück M, Frey WO, et al (2022). Association of gene variants for me-chanical and metabolic muscle quality with cardiorespiratory and muscular var-iables related to performance in skiing athletes. Genes (Basel), 13(10):1798.
31. Akça F, Akalan C, Koz M, et al (2010). In-vestigation of oxygen consumption and lactate profiles in Turkish elite junior rowers. Spormetre, 8(2):77-80.
32. Williams CJ, Williams MG, Eynon N, et al (2017). Genes to predict VO2max train-ability: a systematic review. BMC Ge-nomics, 18(Suppl 8):131.
33. Kimura T, Mącznik AK, Kinoda A, et al (2024). Prevalence of and factors associ-ated with sports injuries in 11,000 Japa-nese collegiate athletes. Sports (Basel), 12(1):10.
34. Werner T, Michel-Kröhler A, Berti S, et al (2023). Not all injuries are the same: dif-ferent patterns in sports injuries and their psychosocial correlates. Sports (Ba-sel), 11(12):237.
35. Goodlin GT, Roos AK, Roos TR, et al (2015). Applying personal genetic data to injury risk assessment in athletes. PLoS One, 10(4):e0122676.
36. Youn BY, Ko SG, Kim JY (2021). Genetic basis of elite combat sports athletes: a systematic review. Biol Sport, 38(4):667-675.
37. Akazawa N, Ohiwa N, Shimizu K, et al (2022). The association of ACTN3 R577X polymorphism with sports speci-ficity in Japanese elite athletes. Biol Sport, 39(4):905-911.
38. Coso JD, Moreno V, Gutiérrez-Hellín J, et al (2019). ACTN3 R577X genotype and exercise phenotypes in recreational marathon runners. Genes (Basel), 10(6):413.
39. Ginszt M, Michalak-Wojnowska M, Gawda P, et al (2018). ACTN3 genotype in pro-fessional sport climbers. J Strength Cond Res, 32(5):1311-1315.
40. Koku FE, Karamızrak SO, Çıftçı AS, et al (2019). The relationship between ACTN3 R577X gene polymorphism and physical performance in amateur soccer players and sedentary individuals. Biol Sport, 36(1):9-16.
41. Deschamps CL, Connors KE, Klein MS, et al (2015). The ACTN3 R577X polymor-phism is associated with cardiometabol-ic fitness in healthy young adults. PLoS One, 10(6):e0130644.
42. Gasser B, Frey WO, Valdivieso P, et al (2023). Association of gene variants with seasonal variation in muscle strength and aerobic capacity in elite skiers. Genes (Basel), 14(6):1165.
43. Moreno V, Areces F, Ruiz-Vicente D, et al (2020). Influence of the ACTN3 R577X genotype on the injury epidemiology of marathon runners. PLoS One, 15(1):e0227548.
44. Gutiérrez-Hellín J, Baltazar-Martins G, Aguilar-Navarro M, et al (2021). Effect of ACTN3 R577X genotype on injury epidemiology in elite endurance run-ners. Genes (Basel), 12(1):76.
45. Kahya S (2023). Investigation of the rela-tionship between ACTN3 (rs1815739) gene and non-contact sports injuries. Spormetre, 21(4):145-157.
46. Mägi A, Unt E, Prans E, et al (2016). The as-sociation analysis between ACE and ACTN3 genes polymorphisms and en-durance capacity in young cross-country skiers: Longitudinal study. J Sports Sci Med, 15(2):287-94.
47. Johansen JM, Goleva-Fjellet S, Sunde A, et al (2020). No change – no gain; the ef-fect of age, sex, selected genes and train-ing on physiological and performance adaptations in Cross-Country Skiing. Front Physiol, 11:581339.
48. Orysiak J, Zmijewski P, Klusiewicz A, et al (2013). The association between ACE gene variation and aerobik capacity in winter endurance disciplines. Biol Sport, 30(4):249-53.
49. Heffernan SM, Kilduff LP, Erskine RM, et al (2016). Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and play-ing position. Physiol Genomics, 48(3):196-201.
2. Végh D, Reichwalderová K, Slaninová M, et al (2022). The effect of selected pol-ymorphisms of the ACTN3, ACE, HIF1A and PPARA genes on the imme-diate supercompensation training effect of elite Slovak endurance runners and football players. Genes (Basel), 13(9):1525.
3. Almeida KY, Cetolin T, Marrero AR, et al (2022). A pilot study on the prediction of non-contact muscle injuries based on ACTN3 R577X and ACE I/D polymor-phisms in professional soccer athletes. Genes (Basel), 13(11):2009.
4. Manning JT, Fink B (2020). Understanding COVID-19: A hypothesis regarding digit ratio (2D:4D), ACE I/D polymorphism, oxygen metabolism and national case fatality rates. Early Hum Dev, 151:10561.
5. Vostrikova A, Pechenkina V, Danilova M, et al (2022). Gene polymorphism and to-tal genetic score in martial arts athletes with different athletic qualifications. Genes (Basel), 13(9):1677.
6. Ortiz AM, Laguarta-Val S, Varillas-Delgado D (2021). Muscle work and its relation-ship with ACE and ACTN3 polymor-phisms are associated with the im-provement of explosive strength. Genes (Basel), 12(8):1177.
7. Maffulli N, Margiotti K, Longo UG, et al (2013). The genetics of sports injuries and athletic performance. Muscles Liga-ments Tendons J, 3(3):173-89.
8. Goleva-Fjellet S, Bjurholt AM, Kure EH, et al (2020). Distribution of allele frequen-cies for genes associated with physical activity and/or physical capacity in a homogenous Norwegian cohort- a cross-sectional study. BMC Genet, 21(1):8.
9. Kumagai H, Miller B, Kim SJ, et al (2023). Novel insights into mitochondrial DNA: Mitochondrial microproteins and mtDNA variants modulate athletic per-formance and age-related diseases. Genes (Basel), 14(2):286.
10. Tharabenjasin P, Pabalan N, Jarjanazi H (2019). Association of the ACTN3 R577X (rs1815739) polymorphism with elite power sports: A meta-analysis. PLoS One, 14(5):e0217390.
11. Baltazar-Martins G, Gutiérrez-Hellín J, Aguilar-Navarro M, et al (2020). Effect of ACTN3 genotype on sports perfor-mance, exercise-induced muscle dam-age, and injury epidemiology. Sports (Ba-sel), 8(7):99.
12. Appel M, Zentgraf K, Krüger K, et al (2021). Effects of genetic variation on endur-ance performance, muscle strength, and injury susceptibility in sports: A system-atic review. Front Physiol, 21:12:694411.
13. Edwards AWF, GH Hardy (2008). (1908) and Hardy-Weinberg equilibrium. Genet-ics, 179(3):1143-1150.
14. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting system-atic reviews. BMJ, 372:n71.
15. Higgins JPT, Thomas J, Chandler J, Cump-ston M, Li T, Page MJ, Welch VA edi-tors. Cochrane Handbook for Systemat-ic Reviews of Interventions version 6.5 (updated August 2024). Cochrane, 2024.
16. McGuinness LA, Higgins JPT (2021). Risk-of-bias VISualization (robvis): An R package and shiny web app for visualiz-ing risk-of-bias assessments. Res Synth Methods, 12(1):55-61.
17. Yang S, Lin W, Jia M, et al (2023). Associa-tion between ACE and ACTN3 genes polymorphisms and athletic perfor-mance in elite and sub-elite Chinese youth male football players. PeerJ, 11:e14893.
18. Wei Q (2021). The ACE and ACTN3 poly-morphisms in female soccer athletes. Genes Environ, 43(1):5.
19. Gineviciene V, Jakaitiene A, Aksenov MO, et al (2016). Association analysis of ACE, ACTN3 and PPARGC1A gene poly-morphisms in two cohorts of European strength and power athletes. Biol Sport,33(3):199-206.
20. Onori ME, Pasqualetti M, Moretti G, et al (2022). Genetics and sport injuries: New perspectives for athletic excellence in an Italian court of rugby union players. Genes, 13(6):995.
21. Pasqualetti M, Onori ME, Canu G, et al (2022). The relationship between ACE, ACTN3 and MCT1 genetic polymor-phisms and athletic performance in Elite rugby union players: A preliminary study. Genes (Basel), 13(6):969.
22. Kim JH, Jung ES, Kim CH, et al (2014). Ge-netic associations of body composition, flexibility and injury risk with ACE, ACTN3 and COL5A1 polymorphisms in Korean ballerinas. J Exerc Nutrition Bio-chem, 18 (2):205-14.
23. Grenda A, Leońska-Duniec A, Kaczmar-czyk M, et al (2014). Interaction between ACE I/D and ACTN3 R577X polymor-phisms in Polish competitive swimmers. J Hum Kinet, 42:127-36.
24. Bosnyák E, Trájer E, Udvardy A, et al (2015). ACE and ACTN3 genes poly-morphisms among female Hungarian athletes in the aspect of sport disci-plines. Acta Physiologica Hungarica, 102 (4):451-8.
25. Erskine RM, Williams AG, Jones DA, et al (2013). The individual and combined in-fluence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training. Scand J Med Sci Sports, 24(4):642-8.
26. Peña-Vázquez O, Castillo LE, González-Chávez SA, et al (2023). Prevalence of polymorphism and post-training expres-sion of ACTN3 (R/X) and ACE (I/D) genes in crossFit athletes. Int J Environ Res Public Health, 20(5):4404.
27. Romero-Blanco C, Artiga-González MJ, Gómez-Cabello A, et al (2023). Strength and endurance training in older women in relation to ACTN3 R577X and ACE I/D polymorphisms. Int J Environ Res Public Health, 20(5):4404.
28. Galeandro V, Notarnicola A, Bianco A, et al (2017). ACTN3/ACE genotypes and mitochondrial genome in professional soccer players’ performance. J Biol Regul Homeost Agents, 31(1):207-213.
29. Doggun M (2022). Strategic role of genetic testing in direction to sports brach. J Turk Sport Sci, 5(2):155-167.
30. Gasser B, Flück M, Frey WO, et al (2022). Association of gene variants for me-chanical and metabolic muscle quality with cardiorespiratory and muscular var-iables related to performance in skiing athletes. Genes (Basel), 13(10):1798.
31. Akça F, Akalan C, Koz M, et al (2010). In-vestigation of oxygen consumption and lactate profiles in Turkish elite junior rowers. Spormetre, 8(2):77-80.
32. Williams CJ, Williams MG, Eynon N, et al (2017). Genes to predict VO2max train-ability: a systematic review. BMC Ge-nomics, 18(Suppl 8):131.
33. Kimura T, Mącznik AK, Kinoda A, et al (2024). Prevalence of and factors associ-ated with sports injuries in 11,000 Japa-nese collegiate athletes. Sports (Basel), 12(1):10.
34. Werner T, Michel-Kröhler A, Berti S, et al (2023). Not all injuries are the same: dif-ferent patterns in sports injuries and their psychosocial correlates. Sports (Ba-sel), 11(12):237.
35. Goodlin GT, Roos AK, Roos TR, et al (2015). Applying personal genetic data to injury risk assessment in athletes. PLoS One, 10(4):e0122676.
36. Youn BY, Ko SG, Kim JY (2021). Genetic basis of elite combat sports athletes: a systematic review. Biol Sport, 38(4):667-675.
37. Akazawa N, Ohiwa N, Shimizu K, et al (2022). The association of ACTN3 R577X polymorphism with sports speci-ficity in Japanese elite athletes. Biol Sport, 39(4):905-911.
38. Coso JD, Moreno V, Gutiérrez-Hellín J, et al (2019). ACTN3 R577X genotype and exercise phenotypes in recreational marathon runners. Genes (Basel), 10(6):413.
39. Ginszt M, Michalak-Wojnowska M, Gawda P, et al (2018). ACTN3 genotype in pro-fessional sport climbers. J Strength Cond Res, 32(5):1311-1315.
40. Koku FE, Karamızrak SO, Çıftçı AS, et al (2019). The relationship between ACTN3 R577X gene polymorphism and physical performance in amateur soccer players and sedentary individuals. Biol Sport, 36(1):9-16.
41. Deschamps CL, Connors KE, Klein MS, et al (2015). The ACTN3 R577X polymor-phism is associated with cardiometabol-ic fitness in healthy young adults. PLoS One, 10(6):e0130644.
42. Gasser B, Frey WO, Valdivieso P, et al (2023). Association of gene variants with seasonal variation in muscle strength and aerobic capacity in elite skiers. Genes (Basel), 14(6):1165.
43. Moreno V, Areces F, Ruiz-Vicente D, et al (2020). Influence of the ACTN3 R577X genotype on the injury epidemiology of marathon runners. PLoS One, 15(1):e0227548.
44. Gutiérrez-Hellín J, Baltazar-Martins G, Aguilar-Navarro M, et al (2021). Effect of ACTN3 R577X genotype on injury epidemiology in elite endurance run-ners. Genes (Basel), 12(1):76.
45. Kahya S (2023). Investigation of the rela-tionship between ACTN3 (rs1815739) gene and non-contact sports injuries. Spormetre, 21(4):145-157.
46. Mägi A, Unt E, Prans E, et al (2016). The as-sociation analysis between ACE and ACTN3 genes polymorphisms and en-durance capacity in young cross-country skiers: Longitudinal study. J Sports Sci Med, 15(2):287-94.
47. Johansen JM, Goleva-Fjellet S, Sunde A, et al (2020). No change – no gain; the ef-fect of age, sex, selected genes and train-ing on physiological and performance adaptations in Cross-Country Skiing. Front Physiol, 11:581339.
48. Orysiak J, Zmijewski P, Klusiewicz A, et al (2013). The association between ACE gene variation and aerobik capacity in winter endurance disciplines. Biol Sport, 30(4):249-53.
49. Heffernan SM, Kilduff LP, Erskine RM, et al (2016). Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and play-ing position. Physiol Genomics, 48(3):196-201.
| Files | ||
| Issue | Vol 54 No 8 (2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v54i8.19571 | |
| Keywords | ||
| Gene Polymorphism Sports performance | ||
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How to Cite
1.
Kahya S. ACTN3 R577X and ACE I/D Polymorphisms and Sports Performance: A Systematic Review. Iran J Public Health. 2025;54(8):1620-1630.
