Journal of Human Sport and Exercise

Evaluation of ACTN3 R577X and ACE I/D polymorphisms in young Colombian athletes: An exploratory research

Michelle Ortiz, Adis Ayala, Jorge L. Petro, Rodrigo Argothy, Jonny Garzón, Diego A. Bonilla

DOI: https://doi.org/10.14198/jhse.2022.173.14

Abstract

There are genetic sequences that might be associated with improved athletic performance, such as the α-actinin-3 (ACTN3) R577X polymorphism and the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), which are related to phenotypes of increased muscle strength and endurance, respectively. This STREGA-based cross-sectional study compared the genotype and allele frequencies of the ACTN3 R577X and ACE I/D polymorphisms between Colombian athletes (n = 37) and non-athletic controls (n = 37). Genotyping was performed using polymerase chain reaction (PCR) and subsequent enzymatic restriction (RFLP). The distribution of the ACTN3 R577X genotype of control and athletic groups met Hardy–Weinberg Equilibrium (HWE) (all p > .05); however, in the strength-trained athletes, the distribution of the ACE I/D genotype was not found in HWE. In athletic population, genotype distribution and allele frequencies of the ACTN3 R577X (n = 37) was RR: 35.1% (n = 13), RX: 54.1% (n = 20), XX: 10.8% (n = 4), and R: 0.6216 and X: 0.3784, respectively. For ACE I/D (n = 74) it was found a genotype distribution of DD: 35.1% (n = 13), ID: 24.3% (n = 9), II: 40.5% (n = 15), and allelic frequencies of D: 62.16% and I: 37.84%. Statistical analysis showed an association between the ACE genotypes with strength, endurance and control groups (X2 = 15.3, gl = 4, p = .004); however, the ACTN3 R577X polymorphism did not have a significant association (X2 = 3.99, gl = 4, p = .408). Although studies with a more homogeneous and larger sample size are required, the results of this exploratory study contribute to the genotypic characterization of Colombian athletes with the objective of improving the methodologies and its applications to sports medicine.


Keywords

Physical performance; Genetic variants; Sports medicine; Molecular biology; Sports science

References

Ayala, A. (1997). Estudio del gen que codifica la enzima N-Acetil-Galactosamina-6-Sulfato-Sulfatasa en personas normales y pacientes colombianos con la enfermedad de Morquio. (Unpublished master dissertation), Universidad de los Andes, Bogotá, Colombia.

Bell, W., Colley, J., Gwynne, J., Glazier, P., Evans, W. D., & Darlington, S. E. (2010). ACE ID genotype and leg power in rugby union players. Journal of sports medicine and physical fitness, 50(3), 350.

Chiu, Y.-H., Lai, J.-I., Tseng, C.-Y., Wang, S.-H., Li, L.-H., Kao, W.-F., . . . Hsieh, C.-Y. (2019). Impact of angiotension I converting enzyme gene I/D polymorphism on running performance, lipid, and biochemical parameters in ultra-marathoners. Medicine, 98(29), e16476. https://doi.org/10.1097/MD.0000000000016476

Coelho, D., Pimenta, E., Rosse, I., de Castro, B., Becker, L., de Oliveira, E., . . . Garcia, E. (2018). Evidence for a Role of ACTN3 R577X Polymorphism in Football Player's Career Progression. International Journal of Sports Medicine, 39(14), 1088-1093. https://doi.org/10.1055/a-0753-4973

Del Coso, J., Moreno, V., Gutiérrez-Hellín, J., Baltazar-Martins, G., Ruíz-Moreno, C., Aguilar-Navarro, M., . . . Lucía, A. (2019). ACTN3 R577X Genotype and Exercise Phenotypes in Recreational Marathon Runners. Genes, 10(6), 413. https://doi.org/10.3390/genes10060413

Enciso-Castellanos, S. (2006). LDL y receptor β-3 adrenérgico y su correlación con el VO2 pico en individuos sedentarios y entrenados residentes en altura intermedia. (Unpublished master dissertation), Universidad Nacional de Colombia, Bogotá, Colombia.

Eschbach, S., Hofmann, C., Maerz, M., Maier, U. G., & Sitte, P. (1990). Molecular Cloning. A Laboratory Manual. 2. Auflage. Hrsg. von J. Sambrook, EF Fritsch, T. Maniatis, Cold Spring Harbor Laboratory Press, Cold Spring Harbour 1989, $115. ISBN 0‐87969‐309‐6. Biologie in unserer Zeit, 20(6), 285-285. https://doi.org/10.1002/biuz.19900200607

Esparza-Ros, F., Vaquero-Cristóbal, R., & Marfell-Jones, M. (2019). International Standards for Anthropometric Assessment. In. Murcia, Spain: The International Society for the Advancement of Kinanthropometry.

Eynon, N., Duarte, J. A., Oliveira, J., Sagiv, M., Yamin, C., Meckel, Y., . . . Goldhammer, E. (2009). ACTN3R577X Polymorphism and Israeli Top-level Athletes. International Journal of Sports Medicine, 30(09), 695-698. https://doi.org/10.1055/s-0029-1220731

Eynon, N., Hanson, E. D., Lucia, A., Houweling, P. J., Garton, F., North, K. N., & Bishop, D. J. (2013). Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way. Sports Medicine, 43(9), 803-817. https://doi.org/10.1007/s40279-013-0059-4

Falahati, A., & Arazi, H. (2019). Association of ACE gene polymorphism with cardiovascular determinants of trained and untrained Iranian men. Genes and Environment, 41(1). https://doi.org/10.1186/s41021-019-0126-7

Galeandro, V., Notarnicola, A., Bianco, A., Tafuri, S., Russo, L., Pesce, V., . . . Petruzzella, V. (2017). ACTN3/ACE genotypes and mitochondrial genome in professional soccer players performance. Journal of Biological Regulators and Homeostatic Agents, 31(1), 207-213.

Gonzalez, G. E., Ma, F., Yang, Y., Li, X., Zhou, F., Gao, C., . . . Gao, L. (2013). The Association of Sport Performance with ACE and ACTN3 Genetic Polymorphisms: A Systematic Review and Meta-Analysis. PLoS One, 8(1), e54685. https://doi.org/10.1371/journal.pone.0054685

Gunel, T., Gumusoglu, E. C. E., Hosseini, M. K., Yilmazyildirim, E. D. A., Dolekcap, I., & Aydinli, K. (2014). Effect of angiotensin I-converting enzyme and α-actinin-3 gene polymorphisms on sport performance. Molecular Medicine Reports, 9(4), 1422-1426. https://doi.org/10.3892/mmr.2014.1974

Heffernan, S. M., Kilduff, L. P., Erskine, R. M., Day, S. H., McPhee, J. S., McMahon, G. E., . . . Williams, A. G. (2016). Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position. Physiological Genomics, 48(3), 196-201. https://doi.org/10.1152/physiolgenomics.00107.2015

Jacob, Y., Spiteri, T., Hart, N., & Anderton, R. (2018). The Potential Role of Genetic Markers in Talent Identification and Athlete Assessment in Elite Sport. Sports (Basel), 6(3), 88. https://doi.org/10.3390/sports6030088

Jones, N., Kiely, J., Suraci, B., Collins, D., de Lorenzo, D., Pickering, C., & Grimaldi, K. (2016). A genetic-based algorithm for personalized resistance-training. Biology of Sport, 33(2), 117-126.

Kellmann, M., Bertollo, M., Bosquet, L., Brink, M., Coutts, A. J., Duffield, R., . . . Beckmann, J. (2018). Recovery and Performance in Sport: Consensus Statement. International Journal of Sports Physiology and Performance, 13(2), 240-245. https://doi.org/10.1123/ijspp.2017-0759

Kikuchi, N., Miyamoto-Mikami, E., Murakami, H., Nakamura, T., Min, S.-K., Mizuno, M., . . . Fuku, N. (2015). ACTN3R577X genotype and athletic performance in a large cohort of Japanese athletes. Eur J Sport Sci, 16(6), 694-701. https://doi.org/10.1080/17461391.2015.1071879

Koku, F. E., Karamızrak, S. O., Çiftçi, A. S., Taşlıdere, H., Durmaz, B., & Çoğulu, Ö. (2019). The relationship between ACTN3 R577X gene polymorphism and physical performance in amateur soccer players and sedentary individuals. Biology of Sport, 36(1), 9-16. https://doi.org/10.5114/biolsport.2018.78900

Lammi, M. J., 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. https://doi.org/10.1371/journal.pone.0217390

Li, Y., Wang, L. Q., Yi, L., Liu, J., Hu, Y., Lu, Y., & Wang, M. (2017). ACTN3 R577X genotype and performance of elite middle-long distance swimmers in China. Biology of Sport, 1, 39-43. https://doi.org/10.5114/biolsport.2017.63731

Little, J., Higgins, J. P., Ioannidis, J. P., Moher, D., Gagnon, F., von Elm, E., . . . Birkett, N. (2009). Strengthening the reporting of genetic association studies (STREGA): an extension of the strengthening the reporting of observational studies in epidemiology (STROBE) statement. J Clin Epidemiol, 62(6), 597-608 e594. https://doi.org/10.1016/j.jclinepi.2008.12.004

MacArthur, D. G., Seto, J. T., Raftery, J. M., Quinlan, K. G., Huttley, G. A., Hook, J. W., . . . North, K. N. (2007). Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nature Genetics, 39(10), 1261-1265. https://doi.org/10.1038/ng2122

Maciejewska-Skrendo, A., Cięszczyk, P., Chycki, J., Sawczuk, M., & Smółka, W. (2019). Genetic Markers Associated with Power Athlete Status. J Hum Kinet, 68(1), 17-36.

Massidda, M., Bachis, V., Corrias, L., Piras, F., Scorcu, M., Culigioni, C., . . . Calò, C. M. (2015). ACTN3 R577X polymorphism is not associated with team sport athletic status in Italians. Sports Medicine - Open, 1(1). https://doi.org/10.1186/s40798-015-0008-x

Massidda, M., Voisin, S., Culigioni, C., Piras, F., Cugia, P., Yan, X., . . . Calò, C. M. (2019). ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players. Clinical Journal of Sport Medicine, 29(1), 57-61. https://doi.org/10.1097/JSM.0000000000000487

McCauley, T., Mastana, S. S., & Folland, J. P. (2010). ACE I/D and ACTN3 R/X polymorphisms and muscle function and muscularity of older Caucasian men. European Journal of Applied Physiology, 109(2), 269-277. https://doi.org/10.1007/s00421-009-1340-y

McCauley, T., Mastana, S. S., Hossack, J., MacDonald, M., & Folland, J. P. (2009). Human angiotensin-converting enzyme I/D and α-actinin 3 R577X genotypes and muscle functional and contractile properties. Experimental Physiology, 94(1), 81-89. https://doi.org/10.1113/expphysiol.2008.043075

Mills, M., Yang, N., Weinberger, R., Vander Woude, D. L., Beggs, A. H., Easteal, S., & North, K. (2001). Differential expression of the actin-binding proteins, α-actinin-2 and -3, in different species: implications for the evolution of functional redundancy. Human Molecular Genetics, 10(13), 1335-1346. https://doi.org/10.1093/hmg/10.13.1335

Miyamoto, N., Miyamoto-Mikami, E., Hirata, K., Kimura, N., & Fuku, N. (2018). Association analysis of theACTN3R577X polymorphism with passive muscle stiffness and muscle strain injury. Scand J Med Sci Sports, 28(3), 1209-1214. https://doi.org/10.1111/sms.12994

Moreno-Pérez, V., Machar, R., Sanz-Rivas, D., & Del Coso, J. (2020). ACTN3 R577X Genotype in Professional and Amateur Tennis Players. Journal of Strength and Conditioning Research, 34(4), 952-956. https://doi.org/10.1519/JSC.0000000000003501

North, K. N., Yang, N., Wattanasirichaigoon, D., Mills, M., Easteal, S., & Beggs, A. H. (1999). A common nonsense mutation results in α-actinin-3 deficiency in the general population. Nature Genetics, 21(4), 353-354. https://doi.org/10.1038/7675

Orysiak, J., Mazur-Różycka, J., Busko, K., Gajewski, J., Szczepanska, B., & Malczewska-Lenczowska, J. (2018). Individual and Combined Influence of ACE and ACTN3 Genes on Muscle Phenotypes in Polish Athletes. Journal of Strength and Conditioning Research, 32(10), 2776-2782. https://doi.org/10.1519/JSC.0000000000001839

Papadimitriou, I. D., Lockey, S. J., Voisin, S., Herbert, A. J., Garton, F., Houweling, P. J., . . . Eynon, N. (2018). No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes. BMC Genomics, 19(1). https://doi.org/10.1186/s12864-017-4412-0

Papadimitriou, I. D., Lucia, A., Pitsiladis, Y. P., Pushkarev, V. P., Dyatlov, D. A., Orekhov, E. F., . . . Eynon, N. (2016). ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study. BMC Genomics, 17(1). https://doi.org/10.1186/s12864-016-2462-3

Petro, J., Bonilla, DA. (2015). Metabolismo Energético durante el Esfuerzo Físico: hacia una Conceptualización Actual en las Ciencias de la Actividad Física y el Deporte. Paper presented at the XII Congreso Internacional en Ciencias de la Actividad Física y el Deporte, Tijuana, México.

Pickering, C., Kiely, J., Grgic, J., Lucia, A., & Del Coso, J. (2019). Can Genetic Testing Identify Talent for Sport? Genes, 10(12), 972. https://doi.org/10.3390/genes10120972

Ribas, M. R., Oliveira Netto, Z. C., Salgueirosa, F., Fernandes, P., Matos, O. d., & Bassan, J. C. (2017). Association of ACTN3 R577X and ACE I/D polymorphisms in Brazilians wrestlers. Revista Brasileira de Medicina do Esporte, 23, 469-472. https://doi.org/10.1590/1517-869220172306171864

Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P., & Soubrier, F. (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. Journal of Clinical Investigation, 86(4), 1343-1346. https://doi.org/10.1172/JCI114844

Sabir, J. S. M., Omri, A. E., Ali Khan, I., Banaganapalli, B., Hajrah, N. H., Zrelli, H., . . . Khan, M. (2019). ACE insertion/deletion genetic polymorphism, serum ACE levels and high dietary salt intake influence the risk of obesity development among the Saudi adult population. Journal of the Renin-Angiotensin-Aldosterone System, 20(3), 147032031987094. https://doi.org/10.1177/1470320319870945

Sánchez, J., Campuzano, Ó., Iglesias, A., & Brugada, R. (2009). Genética y deporte. Apunts. Medicina de l'Esport, 44(162), 86-97. https://doi.org/10.1016/S1886-6581(09)70114-8

Saunders, C. J., September, A. V., Xenophontos, S. L., Cariolou, M. A., Anastassiades, L. C., Noakes, T. D., & Collins, M. (2007). No Association of the ACTN3 Gene R577X Polymorphism with Endurance Performance in Ironman Triathlons. Annals of Human Genetics, 71(6), 777-781. https://doi.org/10.1111/j.1469-1809.2006.00385.x

Stucky-Byler, L., Rodríguez-Buitrago, A. . (2018). Análisis exploratorio de la relación entre el polimorfismo ACTN3 R577X y el rendimiento deportivo en levantadores de pesas colombianos (Master's thesis), Universidad de Ciencias Aplicadas y Ambientales U.D.C.A., Retrieved from https://repository.udca.edu.co/handle/11158/1056

Valderrama, A., Endo, M. . (2009). Frecuencia y distribución del polimorfismo I/D del gen ACE en adultos jóvenes de la ciudad de Cali. Paper presented at the 10th Colombian Conference of Human Genetics.

Vallejo, D., Guerrero, M., Bejarano, L., Valderrama, A. (2009). Prevalencia de la Mutación R577X del Gen ACTN3 en Adultos Jóvenes de la Ciudad de Cali. Paper presented at the 10th Colombian Conference of Human Genetics.

Vincent, B., De Bock, K., Ramaekers, M., Van den Eede, E., Van Leemputte, M., Hespel, P., & Thomis, M. A. (2007). ACTN3 (R577X) genotype is associated with fiber type distribution. Physiological Genomics, 32(1), 58-63. https://doi.org/10.1152/physiolgenomics.00173.2007

Webborn, N., Williams, A., McNamee, M., Bouchard, C., Pitsiladis, Y., Ahmetov, I., . . . Wang, G. (2015). Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement. British Journal of Sports Medicine, 49(23), 1486-1491. https://doi.org/10.1136/bjsports-2015-095343

Woods, D., Hickman, M., Jamshidi, Y., Brull, D., Vassiliou, V., Jones, A., . . . Montgomery, H. (2001). Elite swimmers and the D allele of the ACE I/D polymorphism. Human Genetics, 108(3), 230-232. https://doi.org/10.1007/s004390100466

World Medical Association. (2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA; 310(20):2191–2194. https://doi.org/10.1001/jama.2013.281053

Yang, N., MacArthur, D. G., Gulbin, J. P., Hahn, A. G., Beggs, A. H., Easteal, S., & North, K. (2003). ACTN3 Genotype Is Associated with Human Elite Athletic Performance. The American Journal of Human Genetics, 73(3), 627-631. https://doi.org/10.1086/377590

Yang, R., Shen, X., Wang, Y., Voisin, S., Cai, G., Fu, Y., . . . Yan, X. (2017). ACTN3 R577X Gene Variant Is Associated With Muscle-Related Phenotypes in Elite Chinese Sprint/Power Athletes. Journal of Strength and Conditioning Research, 31(4), 1107-1115. https://doi.org/10.1519/JSC.0000000000001558

Znazen, H., Mejri, A., Touhami, I., Chtara, M., Siala, H., Ahmetov, I., . . . Soussi, N. (2015). Genetic advantageous predisposition of angiotensin converting enzyme id polymorphism in Tunisian athletes. J Sports Med Phys Fitness, 56(6), 724-730.




DOI: https://doi.org/10.14198/jhse.2022.173.14





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