Genetic Differences in Peroxisome Proliferator-Activated Receptor Alpha Gene in Endurance Athletes (Long Distance Runners) and Power/Endurance Athletes (Wrestlers, Football Players)

Abstract

Introduction: Peroxisome proliferator-activated receptor alpha gene plays an important role in the expression of genes involved in fatty acid, glucose, and energy metabolism. PPARα intron 7 G/C polymorphism (rs4253778) is one of the genes associated with athletic performance. This study aimed to investigate the genotype distribution and allele frequencies of PPARα G/C of endurance-oriented athletes (long-distance runners) and power/endurance-oriented athletes (wrestlers and football players) (n=158) and non-athletic individuals (n=56). Material and Methods: PPARα intron 7 G/C gene polymorphism was analyzed using the polymerase chain reaction and restriction fragment length polymorphism methods. Results: Genotypes and allele frequencies of PPARα intron 7 G/C were compared between endurance-oriented athletes (long-distance runners) and power/endurance-oriented athletes (wrestlers, and football players) categorized according to their sport disciplines. In addition, athletes were compared to non-athletic individuals. The genotype and allele frequencies of PPARα intron 7 G/C were similar in the groups of athlete and non-athletic individuals (p˃0.05). There was no statistically significant association in genotype distribution and allele frequencies of the PPARα gene among endurance-oriented athletes, power/endurance-oriented athletes, and non-athletic individuals (p˃0.05). Conclusion: The PPARα gene polymorphism may not be considered as a distinctive genetic marker in endurance and mixed sport disciplines.

Keywords

• Genetics
• PPARα
• polymorphism
• sports

References

1. 1. Momozawa Y, Mizukami K. Unique roles of rare variants in the genetics of complex diseases in humans. J Hum Genet. 2021;66(1): 11-23. Available from: doi:10.1038/s10038-020-00845-2.
2. 2. Petranović MZ, Erhardt J, Skerbic MM, Jermen N, Korać P. Genome editing and selection based on genes associated with sports athletic performance - some bio-ethical issues. Synth Philos. 2020;34: 323-340. Available from: doi:10.21464/sp34206.
3. 3. Ben-Zaken S, Meckel Y, Nemet D, Eliakim A Genetic score of power-speed and endurance track and field athletes. Scand J Med Sci Spor. 2015;25(2): 166-174. Available from: doi:10.1111/sms.12141.
4. 4. Collins M, September AV, Posthumus M. Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications. Brit J Sport Med. 2015;49(23): 1497-1503. Available from: doi:10.1136/bjsports-2015-095180.
5. 5. De Moor MH, Spector TD, Cherkas LF, et al. Genome-wide linkage scan for athlete status in 700 British female DZ twin pairs. Twin Res Hum Genet. 2007;10(6): 812-20. Available from: doi:10.1375/twin.10.6.812.
6. 6. Tanisawa K, Wang G, Seto J, et al. Sport and exercise genomics: the FIMS 2019 consensus statement update. Brit J Sport Med. 2020;54(16): 969-975. Available from: doi:10.1136/bjsports-2019-101532.
7. 7. Pitsiladis YP, Tanaka M, Eynon N, et al. Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance. Physiol Genomics. 2016;48(3): 183-190. Available from: doi:10.1152/physiolgenomics.00105.2015.
8. 8. Gineviciene V, Pranckeviciene E, Milasius K, Kucinskas V. Relating fitness phenotypes to genotypes in Lithuanian elite athletes. Acta Med Litu. 2010;17: 1-10. Available from: doi:10.2478/v10140-010-0001-0.

9. 9. Santos CG, Pimentel-Coelho PM, Budowle B, et al. The heritable path of human physical performance: from single polymorphisms to the "next generation". Scand J Med Sci Spor. 2015;26(6): 600-612. Available from: doi:10.1111/sms.12503.
10. 10. Gineviciene V, Jakaitiene A, Aksenov MO, et al. Association analysis of ACE, ACTN3 and PPARGC1A gene polymorphisms in two cohorts of European strength and power athletes. Biol Sport. 2016;33(3): 199-206. Available from: doi:10.5604/20831862.1201051.
11. 11. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20(5): 649-688. Available from: doi:10.1210/edrv.20.5.0380.
12. 12. van Raalte DH, Li M, Pritchard PH, Wasan KM. Peroxisome proliferator-activated receptor (PPAR)-alpha: a pharmacological target with a promising future. Pharm Res. 2004;21(9): 1531-1538. Available from: doi:10.1023/b:pham.0000041444.06122.8d.
13. 13. Gulick T, Cresci S, Caira T, Moore DD, Kelly DP. The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci USA. 1994:91(23):11012-11016. Available from: doi:10.1073/pnas.91.23.11012.
14. 14. Maciejewska-Skrendo A, Cięszczyk P, Chycki J, Sawczuk M, Smółka W. Genetic markers associated with power athlete status. J Hum Kinet. 2019;68: 17-36. Available from: doi:10.2478/hukin-2019-0053.
15. 15. Lemberger T, Braissant O, Juge-Aubry C, et al. PPAR tissue distribution and interactions with other hormone-signaling pathways. Ann Ny Acad Sci. 1996;804: 231-251. Available from: doi:10.1111/j.1749-6632.1996.tb18619.x.
16. 16. Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinol. 1996;137(1): 354-366.
17. 17. Lopez-Leon S, Tuvblad C, Forero DA. Sports genetics: the PPARA gene and athletes' high ability in endurance sports. A systematic review and meta-analysis. Biol Sport. 2016;33(1): 3-6. Available from: doi:10.5604/20831862.1180170.
18. 18. Ahmetov II, Williams AG, Popov DV, et al. The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes. Hum Genet. 2009;126(6): 751-761. Available from: doi:10.1007/s00439-009-0728-4.
19. 19. Ahmetov II, Mozhayskaya IA, Flavell DM, et al. PPAR alpha gene variation and physical performance in Russian athletes. Eur J Appl Physiol. 2006;97(1): 103-108. Available from: doi:10.1007/s00421-006-0154-4.
20. 20. Cieszczyk P, Sawczuk M, Maciejewska A, Ficek K, Eider J. Variation in peroxisome proliferator activated receptor α gene in elite combat athletes, Eur J Sport Sci. 2011;11(2): 119-123. Available from: doi:0.1080/17461391.2010.487120.
21. 21. Stastny P, Lehnert M, De Ste Croix M, et al. Effect of COL5A1, GDF5, and PPARA genes on a movement screen and neuromuscular performance in adolescent team sport athletes. J Strength Cond Res. 2019;33(8): 2057-2065. Available from: doi:10.1519/JSC.0000000000003142.
22. 22. Ahmetov II, Gavrilov DN, Astratenkova IV, et al. The association of ACE, ACTN3 and PPARA gene variants with strength phenotypes in middle school-age children. J Physiol Sci. 2013;63(1): 79-85. Available from: doi:10.1007/s12576-012-0233-8.
23. 23. Broos S, Windelinckx A, De Mars G, et al. Is PPARα intron 7 G/C polymorphism associated with muscle strength characteristics in nonathletic young men? Scand J Med Sci Spor. 2013;23(4): 494-500. Available from: doi:10.1111/j.1600-0838.2011.01406.x.
24. 24. Maciejewska A, Sawczuk M, Cieszczyk P. Variation in the PPAR alpha gene in Polish rowers. J. Sci. Med. Sport. 2011;14: 58-64. Available from: doi:10.1016/j.jsams.2010.05.006.
25. 25. Eynon N. Meckel Y. Sagiv M. Yamin C. Amir R. Sagiv M. et al. Do PPARGC1A and PPAR alpha polymorphisms influence sprint or endurance phenotypes? Scand J Med Sci Sports. 2010;20: e145-e150. Available from: doi:10.1111/j.1600-0838.2009.00930.x.
26. 26. Petr M, Stastny P, Pecha O, Šteffl M, Šeda O, Kohlíková E. PPARA intron polymorphism associated with power performance in 30-s anaerobic Wingate Test. PloS one. 2014;9(9): e107171. Available from: doi:10.1371/journal.pone.0107171.
27. 27. Ahmetov, I, Egorova, E, Mustafina L. The PPARA gene polymorphism in team sports athletes. Cent Eur J Sport Sci Med. 2013;1(1): 19-24.
28. 28. Cocci P, Pistolesi L, Guercioni M, Belli L, Carli D, Palermo F. Genetic variants and mixed sport disciplines: a comparison among soccer, combat and motorcycle athletes. Ann Appl Sport Sci. 2019;7: 1-9. Available from: doi:10.29252/aassjournal.7.1.1.
29. 29. Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning–A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press; 1989.
30. 30. Flavell DM, Jamshidi Y, Hawe E, et al. Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease. Circulation. 2002;105(12): 1440-1445. Available from: doi:10.1161/01.cir.0000012145.80593.25.
31. 31. Kesici T, Kocabaş Z. Biyoistatistik. Ankara: Ankara Üniversitesi Eczacılık Fakültesi; 2007.
32. 32. Duval C, Fruchart JC, Staels B. PPAR alpha, fibrates, lipid metabolism and inflammation. Arch Mal Coeur Vaiss. 2004;97: 665-672.
33. 33. Kurtuluş M, Günay M, Cicioğlu İ, et al. Investigation of the relationship between angiotensin converting enzyme (I / D) polymorphism and sportive performance in elite Turkish athletes. Gaziantep Üniversitesi Spor Bilimleri Dergisi. 2018;3(4): 122-137. Available from: doi:10.31680/gaunjss.476196.
34. 34. Petr M, Maciejewska-Skrendo A, Zajac A, Chycki J, Stastny P. Association of elite sports status with gene variants of peroxisome proliferator activated receptors and their transcriptional coactivator. Int J Mol Sci. 2019;21(1):162. Available from: doi:10.3390/ijms21010162.
35. 35. Stølen T, Chamari K, Castagna C, Wisløff U. Physiology of soccer: an update. Sports Med. 2005;35(6): 501-536. Available from: doi:10.2165/00007256-200535060-00004.
36. 36. Ulucan K, Ük Y, Kapıcı S, Yüksel İ, Sercan C, Eken B. Peroxisome proliferator-activated receptor alpha (PPARα) rs4253778 polymorphism in a Turkish soccer player cohort. Pamukkale Journal of Sport Sciences. 2020;11(1): 1-6. Available from: doi: tr/pub/psbd/issue/54773/566534.
37. 37. Akçamlı D, Sipahi S, Yüksel İ, et al. Futbolcularda peroksizom proliferatör – aktive reseptör alfa rs4253778 polimorfizm dağılımının belirlenmesi. Eurasian Research in Sport Science. 2018; 3(2): 75-79. Available from: doi:10.22396/ERISS.2018.37.
38. 38. Gineviciene V, Jakaitiene A, Tubelis L, Kucinskas V. Variation in the ACE, PPARGC1A and PPARA genes in Lithuanian football players. Eur J Sport Sci. 2014;14(Suppl1): 289-295. Available from: doi:10.1080/17461391.2012.691117.
39. 39. Egorova ES, Borisova AV, Mustafina LJ, et al. The polygenic profile of Russian football players. J Sports Sci. 2014;32(13): 1-8. Available from: doi: 10.1080/02640414.2014.898853.
40. 40. Proia P, Bianco A, Schiera G, et al. PPARα gene variants as predicted performance-enhancing polymorphisms in professional Italian soccer players. Open Access J Sports Med. 2014;5: 273-278. Available from: doi:10.2147/OAJSM.S68333.
41. 41. Drozdovska SB, Dosenko VE, Ahmetov II, Ilyin VN. The association of gene polymorphisms with athlete status in Ukrainians. Biol Sport. 2013;30(3): 163-167. Available from: doi:10.5604/20831862.1059168.
42. 42. Johansen JM, Goleva-Fjellet S, Sunde A, et al. No Change - No gain; the effect of age, sex, selected genes and training on physiological and performance adaptations in cross-country skiing. Front Physiol. 2020;11: 581339. Available from: doi:10.3389/fphys.2020.581339.
43. 43. Jones N, Kiely J, Suraci B, et al. A genetic-based algorithm for personalized resistance training. Biol Sport. 2016;33(2): 117-126. Available from: doi:10.5604/20831862.1198210.
44. 44. Tsianos GI, Evangelou E, Boot A, et al. Associations of polymorphisms of eight muscle- or metabolism-related genes with performance in Mount Olympus marathon runners. J Appl Physiol. 2010;108(3): 567-574. Available from: doi: 10.1152/japplphysiol.00780.2009.
45. 45. Mavlyanov I, Parpiev S, Sadikov A, Kurganov S, Makhmudov D. Relative features of the PPARA (Rs4253778), PPARGC1A (Rs8192678) and PPARG2 (Rs1801282) polymorphisms genes in athletes engaged in cyclic types of sports. EJMCM. 2020;7(2): 1860-1869.
46. 46. Tural E, Kara N, Agaoglu SA, Elbistan M, Tasmektepligil MY, Imamoglu O. PPAR-α and PPARGC1A gene variants have strong effects on aerobic performance of Turkish elite endurance athletes. Mol Biol Rep. 2014; 41(9): 5799-5804. Available from: doi: 10.1007/s11033-014-3453-6.