Türk Futbolcularda Alfa- Aktinin-3 (ACTN3) Ve Anjiyotensin Dönüştürücü Enzim (ACE) Polimorfizmleri Atletik Performans için Bir Biyobelirteç Olabilir mi?

Abstract

Alfa- aktinin-3 (ACTN3) ve anjiyotensin dönüştürücü enzim (ACE) genleri atletik performans ile ilgili incelenen genler arasında yer almaktadır. Çalışmamızda, atletik performans üzerine etkisi olduğu düşünülen ACTN3 rs1815739 ve ACE gen polimorfizlerinin dağılımlarını belirlemeyi amaçladık. Çalışmamıza aynı antrenman programı uygulayan 15-29 yaş arası 21 profesyonel futbolcu ve 105 kontrol grubu katıldı. Sporculardan alınan ağız içi epitel hücrelerinden DNA izolasyonu gerçekleştirildi. ACTN3 genotiplendirmesi için Real-time PCR, ACE genotiplendirmesi için ise polimeraz zincir reaksiyon tekniği kullanılmıştır. ACTN3 rs1815739 polimorfizmi için CC, CT, TT genotip dağılımı sporcularda sırasıyla %28,6, %38,1, %33,3; kontrol grubunda ise %25,7, %34,3, %40,0 bulunmuştur. İki grup arasında genotip dağılımı açısından istatistiksel olarak anlamlı fark yoktu (p=0,8491). Allelik dağılımları incelendiğinde sporcularda %47,6 C alleli, %52,4 T alleli; kontrol grubunda ise %42,9 C, %57,1 T alleli belirlenmiştir. İki grup arasında allelik dağılımı açısından istatistiksel olarak anlamlı fark yoktu (p=0,5700). ACE polimorfizmi incelendiğinde ise DD, ID, II genotipleri sporcularda sırasıyla %19, %38,1, %42,9; kontrol grubunda ise %33,3, %38,1, %28,6 bulunmuştur. İki grup arasında genotip dağılımı açısından istatistiksel olarak anlamlı fark yoktu (p=0,3154). Allelik dağılımları incelendiğinde sporcularda %38,1 D alleli, %61,9 I alleli; kontrol grubunda ise %52,4 D, %47,6 I alleli belirlenmiştir. İki grup arasında allelik dağılımı açısından istatistiksel olarak anlamlı fark yoktu (p=0,0910). Çalışma kohortumuzda, dayanıklılık fenotipi ile ilişkili olan ACTN3 T allelinin, kas dayanıklılığı ile ilişkili olan ACE I allelinin daha baskın olduğu saptanmıştır. ACTN3 ve ACE gen polimorfizmi arasında haplogrupları karşılaştırdığımızda CT+ID’ nin daha yüksek olduğu belirlenmiştir. Futbolcular üzerinde gerçekleştirilen çalışmamızın bundan sonra yapılacak olan çalışmalara öncülük edeceğini düşünmekteyiz.

Keywords

• ACNT3
• ACE
• polimorfizm
• genetik
• spor
• futbol

Could Alpha-Actin-3 (ACTN3) and Angiotensin Converting Enzyme (ACE) Polymorphisms Be a Biomarker for Athletic Performance in Turkish Football Players?

Abstract

Alpha-actinin-3 (ACTN3) and angiotensin-converting enzyme (ACE) genes are among the genes examined for athletic performance. In our study, we aimed to determine the distributions of ACTN3 rs1815739 and ACE gene polymorphisms, which are thought to have an effect on athletic performance. 21 professional football players between the ages of 15-29 who applied the same training program and 105 control group participated in our study. DNA isolation was performed from intraoral epithelial cells taken from athletes. Real-time PCR was used for ACTN3 genotyping and polymerase chain reaction technique was used for ACE genotyping. The CC, CT, TT genotype distribution for ACTN3 rs1815739 polymorphism was 28.6%, 38.1%, 33.3% in athletes, respectively; In the control group, it was found 25.7%, 34.3%, 40.0%. There was no statistically significant difference between the two groups in terms of genotype distribution (p=0.8491). When the allelic distributions are examined, 47.6% C allele and 52.4% T allele in athletes; In the control group, 42.9% C and 57.1% T alleles were determined. There was no statistically significant difference between the two groups in terms of allelic distribution (p=0.5700). When the ACE polymorphism was examined, DD, ID, II genotypes were found in 19%, 38.1%, and 42.9%, respectively, in athletes; in the control group, it was found to be 33.3%, 38.1%, and 28.6%. There was no statistically significant difference between the two groups in terms of genotype distribution (p=0.3154). When the allelic distributions are examined, 38.1% D allele, 61.9% I allele; In the control group, 52.4% D and 47.6% I alleles were determined. There was no statistically significant difference between the two groups in terms of allelic distribution (p=0.0910). In our study cohort, the ACTN3 T allele associated with the endurance phenotype was found to be more dominant than the ACE I allele associated with the muscular endurance. When we compared haplogroups between ACTN3 and ACE gene polymorphism, it was determined that CT+ID was higher. We think that our study on football players will lead to future studies.

Keywords

• ACNT3
• ACE
• polymorphism
• genetics
• sports
• football

References

1. Akkoç, O., Sercan, C., Kırandı, Özlem, Erol, M., Kapıcı, S., Kayhan, R. F., Akkoç, T., & Ulucan, K. . (2020). Determination of the Distribution Angiotensin-Converting Enzyme (ACE I/D) and Alpha-Actinin-3 (ACTN-3 R577X) among Elite Sprinters and Middle-Long Distance Runners in Turkey. Progress in Nutrition, 22(2-S), e2020031. https://doi.org/10.23751/pn.v22i2-S.10640
2. Alfred, T., Ben-Shlomo, Y., Cooper, R., Hardy, R., Cooper, C., Deary, I.J., Gunnell, D., Harris, S.E., Kumari, M., Martin, R.M., Moran, C.N., Pitsiladis, Y.P., Ring, S.M., Sayer, A.A., Smith, G.D., Starr, J.M., Kuh, D., Day, I. N., & HALCyon study team (2011). ACTN3 genotype, athletic status, and life course physical capability: meta-analysis of the published literature and findings from nine studies. Human mutation, 32(9), 1008–1018. https://doi.org/10.1002/humu.21526
3. Alvarez, R., Terrados, N., Ortolano, R., Iglesias-Cubero, G., Reguero, J.R., Batalla, A., Cortina, A., Fernández-García, B., Rodríguez, C., Braga, S., Alvarez, V., & Coto, E. (2000). Genetic variation in the renin-angiotensin system and athletic performance. European journal of applied physiology, 82(1-2), 117–120. https://doi.org/10.1007/s004210050660
4. Amir, O., Amir, R., Yamin, C., Attias, E., Eynon, N., Sagiv, M., Sagiv, M., & Meckel, Y. (2007). The ACE deletion allele is associated with Israeli elite endurance athletes. Experimental physiology, 92(5), 881–886. https://doi.org/10.1113/expphysiol.2007.038711
5. Cerit, M. ve Çakiroğlu, T. (2019). Genetik ve Atletik Performans.TURAN: Stratejik Arastirmalar Merkezi, 11(43), 494-500. http://dx.doi.org/10.15189/1308-8041
6. Coelho, D.B., Pimenta, E.M., Rosse, I.C., Veneroso, C., Pussieldi, G.A., Becker, L.K., Oliveira, E.C., Carvalho, M., & Silami-Garcia, E. (2019). Alpha-Actinin-3 R577X Polymorphism Influences Muscle Damage and Hormonal Responses After a Soccer Game. Journal of strength and conditioning research, 33(10), 2655–2664. https://doi.org/10.1519/JSC.0000000000002575
7. Costerousse, O., Allegrini, J., Lopez, M., & Alhenc-Gelas, F. (1993). Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. The Biochemical journal, 290 ( Pt 1)(Pt 1), 33–40. https://doi.org/10.1042/bj2900033
8. Çiloğlu, F. (2001). Ace Gen Polimorfizminin Uzun Mesafe Koşucuları, Sprinter, Futbolcular Ve Sedanter Popülasyonda Karşılaştırılması. Marmara Üniversitesi Sağlık Bilimleri Enstitüsü.

9. De Mello Costa, M.F. ve Slocombe, R. (2012). The use of Angiotensin-I converting enzyme i/d genetic polymorphism as a biomarker of athletic performance in humans. Biosensors, 2(4), 396–404. https://doi.org/10.3390/bios2040396
10. Eken, B.F., Gezmiş, H., Sercan, C., Kapıcı, S.,Chousein, Ö.M., Kıraç, D., & Ulucan, K. (2018). Türk Atletlerde DVitamini Reseptör Geni Fok1 (rs2228570) ve Bsm1 (rs1544410) Polimorfizmlerinin Analizi. İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi, (6), 561-572. https://doi.org/10.38079/igusabder.453412
11. Eroğlu, O., Zileli, R., Nalbant, M. A., & Ulucan, K. (2018). Prevalence of alpha actinin-3 gene (ACTN3) R577X and angiotensin converting enzyme (ACE) insertion / deletion gene polymorphisms in national and amateur Turkish athletes. Cellular and Molecular Biology, 64(5), 24–28. https://doi.org/10.14715/cmb/2018.64.5.4
12. Eynon, N., Duarte, J.A., Oliveira, J., Sagiv, M., Yamin, C., Meckel, Y., Sagiv, M., & Goldhammer, E. (2009). ACTN3 R577X polymorphism and Israeli top-level athletes. International journal of sports medicine, 30(9), 695–698. https://doi.org/10.1055/s-0029-1220731
13. Gayagay, G., Yu, B., Hambly, B., Boston, T., Hahn, A., Celermajer, D.S., & Trent, R.J. (1998). Elite endurance athletes and the ACE I allele--the role of genes in athletic performance. Human genetics, 103(1), 48–50. https://doi.org/10.1007/s004390050781
14. Gunel, T., Gumusoglu, E., Hosseini, M.K., Yilmazyildirim, E., Dolekcap, I., & Aydinli, K. (2014). Effect of angiotensin I-converting enzyme and α-actinin-3 gene polymorphisms on sport performance. Molecular Medicine Reports, 9, 1422-1426. https://doi.org/10.3892/mmr.2014.1974
15. Holdys, J., Kryściak, J., Stanisławski, D. & Gronek, P. (2011). ACE I/D Gene Polymorphism in Athletes of Various Sports Disciplines. Human Movement, 12(3), 223–231. https://doi.org/10.2478/v10038-011-0022-x
16. Jacob, Y., Hart, N.H., Cochrane, J.L., Spiteri, T., Laws, S.M., Jones, A., Rogalski, B., Kenna, J., & Anderton, R.S. (2020). ACTN3 (R577X) Genotype Is Associated With Australian Football League Players. Journal of Strength and Conditioning Research. https://doi.org/10.1519/JSC.0000000000003458
17. Kasımay, O., Sevinç, D., İşeri, O., Ulucan, K., Unal, M., & Guney, A.İ. (2009).Skeletal muscle gene ACTN3 and physicalperformance: genotype – phenotype corelation. Journal of Sports Science and Medicine Suppl, 11, 121.
18. Kavas, N.C., Yüksel, İ., Sercan, C., Kapıcı, S., Tuna G., & Ulucan, K. (2018). Profesyonel Monopalet Sporcularında Alfa-Aktinin–3 (ACTN3) R577X (rs1815739) Polimorfizminin Dağılımı ve Boy-Kilo İlişkisi. Eurasian Research in Sport Science, 3(1), 26-31. https://doi.org/26-31. 10.22396/ERISS.2018.33
19. Lek, M., Quinlan, K.G., & North, K.N. (2010). The evolution of skeletal muscle performance: gene duplication and divergence of human sarcomeric alpha-actinins. BioEssays : news and reviews in molecular, cellular and developmental biology, 32(1), 17–25. https://doi.org/10.1002/bies.200900110
20. Lippi, G., Longo, U.G., & Maffulli, N. (2010). Genetics and sports. British medical bulletin, 93, 27–47. https://doi.org/10.1093/bmb/ldp007
21. Massidda, M., Bachis, V., Corrias, L., Piras, F., Scorcu, M., Culigioni, C., Masala, D., & Calò, C.M. (2015). ACTN3 R577X polymorphism is not associated with team sport athletic status in Italians. Sports medicine - open, 1(1), 6. https://doi.org/10.1186/s40798-015-0008-x
22. McAuley, A.B.T., Hughes, D.C, Tsaprouni, L.G., Varley, I., Suraci, B., Roos, T.R., Herbert, A.J., & Kelly, A.L. (2021). The association of the ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: a systematic review and meta-analysis. J Sports Sci, 39(2), 200-211. https://doi.org/10.1080/02640414.2020.1812195
23. Moraga Muñoz, R., Caniuqueo Vargas, A., Monsalves-Alvarez, M., Cresp Barría, M., Hernández Mosqueira, C., Roquetti Fernandes, P., & Fernandes Filho, J. (2021). Somatotipo y polimorfismo del gen ACTN3 y ECA en jugadores de tenis de mesa chilenos (Somatotype and polymorphism of the ACTN3 and ACE gene in Chilean table tennis players). Retos, 41, 791-797. https://doi.org/10.47197/retos.v41i0.81410
24. Murphy, A. ve Young, P.W. (2015). The actinin family of actin cross-linking proteins –a genetic perspective. Cell & Bioscience, 5, 49. https://doi.org/10.1186/s13578-015-0029-7
25. Mutlucan, H., Bıyıklı, T., Eken, B.F., Sercan, C., Kapıcı, S., & Ulucan, K. (2017). Türk Profesyonel Futbolcularda Alfa-Aktinin-3 R577 X Polimorfizminin İncelenmesi. Marmara Üniversitesi Spor Bilimleri Dergisi, 2(2), 1-7. https://doi.org/ 10.22396/sbd.2017.26
26. Otey, C.A. ve Carpen, O. (2004) Alpha-actinin revisited: a fresh look at an old player. Cell Motil Cytoskeleton, 58, 104-11. https://doi.org/10.1002/cm.20007
27. Papadimitriou, I.D., Papadopoulos, C., Kouvatsi, A., & Triantaphyllidis, C. (2008). The ACTN3 gene in elite Greek track and field athletes. International journal of sports medicine, 29(4), 352–355. https://doi.org/10.1055/s-2007-965339
28. Pimenta, E.M., Coelho, D.B., Veneroso, C.E., Barros Coelho, E.J., Cruz, I.R., Morandi, R.F., De A Pussieldi, G., Carvalho, M.R., Garcia, E.S., & De Paz Fernández, J.A. (2013). Effect of ACTN3 gene on strength and endurance in soccer players. Journal of strength and conditioning research, 27(12), 3286–3292. https://doi.org/10.1519/JSC.0b013e3182915e66
29. Polat, T., Dogan, C.S., Dogan, M., Akçay, T., & Ulucan, K. (2020). Distribution of α actinin 3 rs1815739 and angiotensin 1 converting enzyme InDel polymorphisms in Turkish bodybuilders. Biomedical Reports, 13(6), 67. https://doi.org/10.3892/br.2020.1374
30. Seto, J.T., Quinlan, K.G., Lek, M., Zheng, X.F., Garton, F., MacArthur, D.G., Hogarth, M.W., Houweling, P.J., Gregorevic, P., Turner, N., Cooney, G.J., Yang, N., & North, K.N. (2013). ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. The Journal of clinical investigation, 123(10), 4255–4263. https://doi.org/10.1172/JCI67691
31. Süel, E. ve Pehlivan, A. (2015). Angiotension dönüştürücü (Converting) Enzim (ACE) gen polimorfizminin elit basketbolcu ve voleybolcularda karşılaştırılması . International Journal of Sport Exercise and Training Sciences - IJSETS , 1(1) , 40-50 . https://doi.org/10.18826/ijsets.93587
32. Şahin, İ. (2005). Angiotensin Dönüştürücü Enzim (ACE) Gen Polimorfizminin Elit Güreşçiler Ve Normal Populasyonda Karşılaştırılması, Marmara Üniversitesi Sağlık Bilimleri Enstitüsü, Doktara Tezi, İstanbul.
33. Şanlısoy, F., Altıntaş, N., Büyükyazı, G., & Candan, N. (2011). Ege bölgesi elit sporcularının ACTN3 R577X genotip dağılımının araştırılması. Cumhuriyet Medical Journal, 33, 153-159.
34. Tacal Aslan, B., Yılmaz, Ö.Ö., Polat, T., Şılar, Ç., Eken, B.F., Sercan Doğan, C. & Ulucan, K. (2021). Distribution of Dopamine Receptor 2 DRD2 rs1800497 Polymorphisms in Professional Football Players . Turkish Journal of Sport and Exercise , 23 (2) , 185-189 . https://doi.org/ 10.15314/tsed.905202
35. Tobina, T., Michishita, R., Yamasawa, F., Zhang, B., Sasaki, H., Tanaka, H., & Kiyonaga, A. (2010). Association between the angiotensin I-converting enzyme gene insertion/deletion polymorphism and endurance running speed in Japanese runners. The Journal of Physiological Sciences, 60(5), 325-330. https://doi.org/10.1007/s12576-010-0100-4
36. Ulucan K. ve Gole S. (2014b). ACE I/D Polymorphism Determination in Turkish Elite Wind-surfers. Sport Science Review, 23(1-2),79-84. https://doi.org/10.2478/ssr-2014-0005
37. Ulucan, K. (2016). Spor Genetiği Açısından Türk Sporcuların ACTN3 R577X Polimorfizm Literatür Özeti . Clinical and Experimental Health Sciences , 6 (1) , 44-47 . https://doi.org/10.5152/clinexphealthsci.2016.059
38. Ulucan, K. , Çam, N. , Sercan, C. , Akbaş, B. , Uyumaz, F. & Yalcın, S. (2015b). Genç Basketbolcularda Anjiotensin Dönüştürücü Enzim (ACE I/D) ve Alfa- Aktinin-3 (ACTN3 R577X) Gen Polimorfizmlerinin Belirlenmesi İçin Pilot Bir Çalışma . Spor Bilimleri Dergisi , 26 (2) , 44-50. https://doi.org/10.17644/sbd.237575
39. Ulucan, K., Bayyurt, G.M., Konuk, M., & Güney, A.İ. (2014a). Effect of alpha-actinin-3 gene on Turkish trained and untrained middle school children’s sprinting performance: a pilot study. Biological Rhythm Research, 45(4), 509-514. https://doi.org/10.1080/09291016.2013.867628
40. Ulucan, K., Ciloglu, F., Sesal, C., Ergeç, D., Kıraç, D., Şahin, İ., Süel,E., & Güney, A.İ. (2009). ACTN3 Gene R577X Polymorphism in Turkish Sprint/Power Athletes. Medimedgen Abstract Book, 33.
41. Ulucan, K., Sercan, C., & Biyikli, T. (2015a). Distribution of Angiotensin-1 Converting Enzyme Insertion/Deletion and α-Actinin-3 Codon 577 Polymorphisms in Turkish Male Soccer Players. Genetics & epigenetics, 7, 1–4. https://doi.org/10.4137/GEG.S31479
42. Ulucan, K., Yalçın, S., Akbaş, B., & Konuk, M. (2014c). Analysis of Solute Carrier Family 6 Member 4 Gene promoter polymorphism in young Turkish basketball players. The Journal of Neurobehavioral Sciences, 1,:37-40.
43. Wei, Q. (2021). The ACE and ACTN3 polymorphisms in female soccer athletes. Genes and Environ 43, 5. https://doi.org/10.1186/s41021-021-00177-3
44. Woods, D.R., Humphries, S.E., & Montgomery, H.E. (2000). The ACE I/D polymorphism and human physical performance. Trends in endocrinology and metabolism: TEM, 11(10), 416–420. https://doi.org/10.1016/s1043-2760(00)00310-6
45. Zilberman-Schapira, G., Chen, J., & Gerstein, M. (2012). On sports and genes. Recent patents on DNA & gene sequences, 6(3), 180–188. https://doi.org/10.2174/187221512802717367