The Genetic Association with Athlete Status, Physical Performance, and Injury Risk in Soccer

Abstract

The aim of this review was to critically appraise the literature concerning the genetic association with athlete status, physical performance, and injury risk in soccer. The objectives were to provide guidance on which genetic markers could potentially be used as part of future practice in soccer and to provide direction for future research in this area. The most compelling evidence identified six genetic polymorphisms to be associated with soccer athlete status (ACE I/D; ACTN3 rs1815739; AGT rs699; MCT1 rs1049434; NOS3 rs2070744; PPARA rs4253778), six with physical performance (ACTN3 rs1815739; AMPD1 rs17602729; BDNF rs6265; COL2A1 rs2070739; COL5A1 rs12722; NOS3 rs2070744), and seven with injury risk (ACTN3 rs1815739; CCL2 rs2857656; COL1A1 rs1800012; COL5A1 rs12722; EMILIN1 rs2289360; IL6 rs1800795; MMP3 rs679620). As well as replication by independent groups, large-scale genome-wide association studies are required to identify new genetic markers. Future research should also investigate the physiological mechanisms associating these polymorphisms with specific phenotypes. Further, researchers should investigate the above associations in female and non-Caucasian soccer players, as almost all published studies have recruited male participants of European ancestry. Only after robust, independently replicated genetic data have been generated, can genetic testing be considered an additional tool to potentially inform future practice in soccer.

Key words

SNP - polymorphism - DNA - injuries - football - physical performance

• References

• 1 Arnason A, Sigurdsson SB, Gudmundsson A. et al. Risk factors for injuries in football. Am J Sports Med 2004; 32: 5S-16S
• 2 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: 812-820
• 3 Hakim AJ, Cherkas LF, Spector TD. et al. Genetic associations between frozen shoulder and tennis elbow: a female twin study. Rheumatology (Oxford) 2003; 42: 739-742
• 4 Magnusson K, Turkiewicz A, Hughes V. et al. High genetic contribution to anterior cruciate ligament rupture: Heritability ~69. Br J Sports Med 2020;
• 5 Bouchard C, An P, Rice T. et al. Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol (1985) 1999; 87: 1003-1008
• 6 Peeters MW, Thomis MA, Loos RJ. et al. Heritability of somatotype components: a multivariate analysis. Int J Obes (Lond) 2007; 31: 1295-1301
• 7 Simoneau JA, Bouchard C. Genetic determinism of fiber type proportion in human skeletal muscle. FASEB J 1995; 9: 1091-1095
• 8 Zhai G, Ding C, Stankovich J. et al. The genetic contribution to longitudinal changes in knee structure and muscle strength: a sibpair study. Arthritis Rheum 2005; 52: 2830-2834
• 9 Brownlee TE, Murtagh CF, Naughton RJ. et al. Isometric maximal voluntary force evaluated using an isometric mid-thigh pull differentiates English Premier League youth soccer players from a maturity-matched control group. Sci Med Football 2018; 2: 209-215
• 10 Murtagh CF, Brownlee TE, OʼBoyle A. et al. Importance of speed and power in elite youth soccer depends on maturation status. J Strength Cond Res 2018; 32: 297-303
• 11 Murtagh CF, Nulty C, Vanrenterghem J. et al. The neuromuscular determinants of unilateral jump performance in soccer players are direction-specific. Int J Sports Physiol Perform 2018; 13: 604-611
• 12 Murtagh CF, Stubbs M, Vanrenterghem J. et al. Patellar tendon properties distinguish elite from non-elite soccer players and are related to peak horizontal but not vertical power. Eur J Appl Physiol 2018; 118: 1737-1749
• 13 Murtagh CF, Vanrenterghem J, O'Boyle A. et al. Unilateral jumps in different directions: a novel assessment of soccer-associated power?. J Sci Med Sport 2017; 20: 1018-1023
• 14 Abbott W, Clifford T. The influence of muscle strength and aerobic fitness on functional recovery in professional soccer. J Sports Med Phys Fitness 2022; 61: 1623-1629 Epub 2021 Dec 9
• 15 Buchheit M, Simpson BM, Hader K. et al. Occurrences of near-to-maximal speed-running bouts in elite soccer: insights for training prescription and injury mitigation. Sci Med Footb 2021; 5: 105-110
• 16 Dos'Santos T, Cowling I, Challoner M. et al. What are the significant turning demands of match play of an English Premier League soccer team?. J Sports Sci 2022; 40: 1750-1759
• 17 Manzi V, Annino G, Savoia C. et al. Relationship between aerobic fitness and metabolic power metrics in elite male soccer players. Biol Sport 2022; 39: 599-606
• 18 Arnason A, Sigurdsson SB, Gudmundsson A. et al. Physical fitness, injuries, and team performance in soccer. Med Sci Sports Exerc 2004; 36: 278-285
• 19 Carling C, Orhant E, LeGall F. Match injuries in professional soccer: inter-seasonal variation and effects of competition type, match congestion and positional role. Int J Sports Med 2010; 31: 271-276
• 20 Ekstrand J, Hägglund M, Waldén M. Injury incidence and injury patterns in professional football: the UEFA injury study. Br J Sports Med 2011; 45: 553-558
• 21 Hawkins RD, Hulse MA, Wilkinson C. et al. The association football medical research programme: an audit of injuries in professional football. Br J Sports Med 2001; 35: 43-47
• 22 Hall ECR, Larruskain J, Gil SM. et al. An injury audit in high-level male youth soccer players from English, Spanish, Uruguayan and Brazilian academies. Phys Ther Sport 2020; 44: 53-60
• 23 Hall ECR, Larruskain J, Gil SM. et al. Playing position and the injury incidence rate in male academy soccer players. J Athl Train 2022; 57: 696-703
• 24 Hall ECR, Larruskain J, Gil SM. et al. Injury risk is greater in physically mature versus biologically younger male soccer players from academies in different countries. Phys Ther Sport 2022; 55: 111-118
• 25 Tabor HK, Risch NJ, Myers RM. Candidate – gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 2002; 3: 391-397
• 26 Seto JT, Quinlan KG, Lek M. et al. ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling. J Clin Invest 2013; 123: 4255-4263
• 27 Erskine RM, Williams AG, Jones DA. et al. The individual and combined influence of ACE and ACTN3 genotypes on muscle phenotypes before and after strength training. Scand J Med Sci Sports 2014; 24: 642-648
• 28 Murtagh CF, Brownlee TE, Rienzi E. et al. The genetic profile of elite youth soccer players and its association with power and speed depends on maturity status. PLoS One 2020; 15: e0234458
• 29 Hall ECR, Baumert P, Larruskain J. et al. The genetic association with injury risk in male academy soccer players depends on maturity status. Scand J Med Sci Sports 2022; 32: 338-350
• 30 Egorova ES, Borisova AV, Mustafina LJ. et al. The polygenic profile of Russian football players. J Sports Sci 2014; 32: 1286-1293
• 31 Gineviciene V, Jakaitiene A, Tubelis L. et al. Variation in the ACE, PPARGC1A and PPARA genes in Lithuanian football players. Eur J Sport Sci 2014; 14: S289-S295
• 32 Juffer P, Furrer R, González-Freire M. et al. Genotype distributions in top-level soccer players: a role for ACE?. Int J Sports Med 2009; 30: 387-392
• 33 Micheli ML, Gulisano M, Morucci G. et al. Angiotensin-converting enzyme/vitamin D receptor gene polymorphisms and bioelectrical impedance analysis in predicting athletic performances of Italian young soccer players. J Strength Cond Res 2011; 25: 2084-2091
• 34 Santiago C, González-Freire M, Serratosa L. et al. ACTN3 genotype in professional soccer players. Br J Sports Med 2008; 42: 71-73
• 35 Ginevičienė V, Pranckevičienė E, Milašius K. et al. Relating fitness phenotypes to genotypes in Lithuanian elite athletes. Acta Medica Lituanica 2010; 17: 1-10
• 36 Pickering C, Suraci B, Semenova EA. et al. A genome-wide association study of sprint performance in elite youth football players. J Strength Cond Res 2019; 33: 2344-2351
• 37 Pimenta EM, Coelho DB, Veneroso CE. et al. Effect of ACTN3 gene on strength and endurance in soccer players. J Strength Cond Res 2013; 27: 3286-3292
• 38 Artells R, Pruna R, Dellal A. et al. Elastin: a possible genetic biomarker for more severe ligament injuries in elite soccer. A pilot study. Muscles Ligaments Tendons J 2016; 6: 188-192
• 39 Ficek K, Cieszczyk P, Kaczmarczyk M. et al. Gene variants within the COL1A1 gene are associated with reduced anterior cruciate ligament injury in professional soccer players. J Sci Med Sport 2013; 16: 396-400
• 40 Larruskain J, Celorrio D, Barrio I. et al. Genetic Variants and hamstring injury in soccer: An association and validation study. Med Sci Sports Exerc 2018; 50: 361-368
• 41 Lulińska-Kuklik E, Rahim M, Domańska-Senderowska D. et al. Interactions between COL5A1 gene and risk of the anterior cruciate ligament rupture. J Hum Kinet 2018; 62: 65-71
• 42 Massidda M, Bachis V, Corrias L. et al. Influence of the COL5A1 rs12722 on musculoskeletal injuries in professional soccer players. J Sports Med Phys Fitness 2015; 55: 1348-1353
• 43 Massidda M, Miyamoto-Mikami E, Kumagai H. et al. Association between the ACE I/D polymorphism and muscle injuries in Italian and Japanese elite football players. J Sports Sci 2020; 38: 2423-2429
• 44 Massidda M, Voisin S, Culigioni C. et al. ACTN3 R577X polymorphism is associated with the incidence and severity of injuries in professional football players. Clin J Sport Med 2019; 29: 57-61
• 45 Pruna R, Artells R, Lundblad M. et al. Genetic biomarkers in non-contact muscle injuries in elite soccer players. Knee Surg Sports Traumatol Arthrosc 2017; 25: 3311-3318
• 46 Pruna R, Artells R, Ribas J. et al. Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: influence on degree of injury and recovery time. BMC Musculoskelet Disord 2013; 14: 221
• 47 Rodas G, Moreno-Pérez V, Del Coso J. et al. Alpha-actinin-3 deficiency might affect recovery from non-contact muscle injuries: Preliminary findings in a top-level soccer team. Genes (Basel) 2021; 12: 769
• 48 Beggs AH, Byers TJ, Knoll JH. et al. Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11. J Biol Chem 1992; 267: 9281-9288
• 49 Ahmetov II, Druzhevskaya AM, Lyubaeva EV. et al. The dependence of preferred competitive racing distance on muscle fibre type composition and ACTN3 genotype in speed skaters. Exp Physiol 2011; 96: 1302-1310
• 50 Vincent B, De Bock K, Ramaekers M. et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics 2007; 32: 58-63
• 51 Bottinelli R, Canepari M, Pellegrino MA. et al. Force-velocity properties of human skeletal muscle fibres: myosin heavy chain isoform and temperature dependence. J Physiol 1996; 495: 573-586
• 52 Gilliver SF, Degens H, Rittweger J. et al. Variation in the determinants of power of chemically skinned human muscle fibres. Exp Physiol 2009; 94: 1070-1078
• 53 Jones DA, Rutherford OM, Parker DF. Physiological changes in skeletal muscle as a result of strength training. Q J Exp Physiol 1989; 74: 233-256
• 54 Ahmetov II, Fedotovskaya ON. Current progress in sports genomics. Adv Clin Chem 2015; 70: 247-314
• 55 Faude O, Koch T, Meyer T. Straight sprinting is the most frequent action in goal situations in professional football. J Sports Sci 2012; 30: 625-631
• 56 Murtagh CF, Naughton RJ, McRobert AP. et al. A coding system to quantify powerful actions in soccer match play: A pilot study. Res Q Exerc Sport 2019; 90: 234-243
• 57 Eynon N, Ruiz JR, Yvert T. et al. The C allele in NOS3 -786 T/C polymorphism is associated with elite soccer player's status. Int J Sports Med 2012; 33: 521-524
• 58 Gómez-Gallego F, Ruiz JR, Buxens A. et al. The -786 T/C polymorphism of the NOS3 gene is associated with elite performance in power sports. Eur J Appl Physiol 2009; 107: 565-569
• 59 Sessa F, Chetta M, Petito A. et al. Gene polymorphisms and sport attitude in Italian athletes. Genet Test Mol Biomarkers 2011; 15: 285-290
• 60 Hopkinson NS, Li KW, Kehoe A. et al. Vitamin D receptor genotypes influence quadriceps strength in chronic obstructive pulmonary disease. Am J Clin Nutr 2008; 87: 385-390
• 61 Dellal A, Chamari K. Wong dP et al. Comparison of physical and technical performance in European soccer match-play: FA Premier League and La Liga. Eur J Sport Sci 2011; 11: 51-59
• 62 Bloomfield J, Polman R, Butterly R. et al. Analysis of age, stature, body mass, BMI and quality of elite soccer players from 4 European Leagues. J Sports Med Phys Fitness 2005; 45: 58-67
• 63 Gomez-Gallego F, Santiago C, González-Freire M. et al. The C allele of the AGT Met235Thr polymorphism is associated with power sports performance. Appl Physiol Nutr Metab 2009; 34: 1108-1111
• 64 Ruiz JR, Arteta D, Buxens A. et al. Can we identify a power-oriented polygenic profile?. J Appl Physiol (1985) 2010; 108: 561-566
• 65 Zarębska A, Sawczyn S, Kaczmarczyk M. et al. Association of rs699 (M235T) polymorphism in the AGT gene with power but not endurance athlete status. J Strength Cond Res 2013; 27: 2898-2903
• 66 Petr M, Maciejewska-Skrendo A, Zajac A. et al. Association of elite sports status with gene variants of peroxisome proliferator activated receptors and their transcriptional coactivator. Int J Mol Sci 2019; 21: 162
• 67 Petr M, Stastny P, Pecha O. et al. PPARA intron polymorphism associated with power performance in 30-s anaerobic Wingate test. PLoS One 2014; 9: e107171
• 68 Sawczuk M, Maciejewska-Karlowska A, Cieszczyk P. et al. Association of the ADRB2 Gly16Arg and Glu27Gln polymorphisms with athlete status. J Sports Sci 2013; 31: 1535-1544
• 69 Massidda M, Mendez-Villanueva A, Ginevičienė V. et al. Association of monocarboxylate transporter-1 (MCT1) A1470TpPolymorphism (rs1049434) with forward football player status. Int J Sports Med 2018; 39: 1028-1034
• 70 Merezhinskaya N, Fishbein WN, Davis JI. et al. Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport. Muscle Nerve 2000; 23: 90-97
• 71 Cupeiro R, Benito PJ, Maffulli N. et al. MCT1 genetic polymorphism influence in high intensity circuit training: a pilot study. J Sci Med Sport 2010; 13: 526-530
• 72 Cupeiro R, Pérez-Prieto R, Amigo T. et al. Role of the monocarboxylate transporter MCT1 in the uptake of lactate during active recovery. Eur J Appl Physiol 2016; 116: 1005-1010
• 73 Aziz AR, Mukherjee S, Chia MY. et al. Validity of the running repeated sprint ability test among playing positions and level of competitiveness in trained soccer players. Int J Sports Med 2008; 29: 833-838
• 74 Di Salvo V, Baron R, Tschan H. et al. Performance characteristics according to playing position in elite soccer. Int J Sports Med 2007; 28: 222-227
• 75 Carling C, Bloomfield J, Nelsen L. et al. The role of motion analysis in elite soccer: contemporary performance measurement techniques and work rate data. Sports Med 2008; 38: 839-862
• 76 Clos E, Pruna R, Lundblad M. et al. ACTN3's R577X single nucleotide polymorphism allele distribution differs significantly in professional football players according to their field position. Med Princ Pract 2021; 30: 92-97
• 77 Petr M, Thiel D, Kateřina K. et al. Speed and power-related gene polymorphisms associated with playing position in elite soccer players. Biol Sport 2022; 39: 355-366
• 78 Viru A, Loko J, Harro M. et al. Critical periods in the development of performance capacity during childhood and adolescence. Eur J Phys Edu 1999; 4: 75-119
• 79 Devismes M, Aeles J, Philips J. et al. Sprint force-velocity profiles in soccer players: impact of sex and playing level. Sports Biomech 2021; 20: 947-957
• 80 Little T, Williams AG. Specificity of acceleration, maximum speed, and agility in professional soccer players. J Strength Cond Res 2005; 19: 76-78
• 81 Mero A. Force-Time Characteristics and running velocity of male sprinters during the acceleration phase of sprinting. Res Q Exerc Sport 1988; 59: 94-98
• 82 Waldron M, Murphy A. A comparison of physical abilities and match performance characteristics among elite and subelite under-14 soccer players. Pediatr Exerc Sci 2013; 25: 423-434
• 83 Venturelli M, Bishop D, Pettene L. Sprint training in preadolescent soccer players. Int J Sports Physiol Perform 2008; 3: 558-562
• 84 Nagano A, Komura T, Fukashiro S. Optimal coordination of maximal-effort horizontal and vertical jump motions – a computer simulation study. Biomed Eng Online 2007; 6: 20
• 85 Fukashiro S, Besier TF, Barrett R. et al. Direction control in standing horizontal and vertical jumps. Int J Sport Health Sci 2005; 3: 272-279
• 86 Ahmetov II, Donnikov AE, Trofimov DY. ACTN3 genotype is associated with testosterone levels of athletes. Biol Sport 2014; 31: 105-108
• 87 Dionísio TJ, Thiengo CR, Brozoski DT. et al. The influence of genetic polymorphisms on performance and cardiac and hemodynamic parameters among Brazilian soccer players. Appl Physiol Nutr Metab 2017; 42: 596-604
• 88 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: 751-761
• 89 Massidda M, Scorcu M, Calò CM. New genetic model for predicting phenotype traits in sports. Int J Sports Physiol Perform 2014; 9: 554-560
• 90 Coelho DB, Pimenta E, Rosse IC. et al. The alpha-actinin-3 r577x polymorphism and physical performance in soccer players. J Sports Med Phys Fitness 2016; 56: 241-248
• 91 Coelho DB, Pimenta EM, Rosse IC. et al. Polymorphism of the angiotensin converting enzyme gene (ACE-I/D) differentiates the aerobic and speed performance of football players. J Sports Med Phys Fitness 2022; 62: 192-198
• 92 Kubo K, Kawakami Y, Fukunaga T. Influence of elastic properties of tendon structures on jump performance in humans. J Appl Physiol (1985) 1999; 87: 2090-2096
• 93 Kubo K, Yata H, Tsunoda N. Effect of gene polymorphisms on the mechanical properties of human tendon structures. Springerplus 2013; 2: 343
• 94 Deprez DN, Fransen J, Lenoir M. et al. A retrospective study on anthropometrical, physical fitness, and motor coordination characteristics that influence dropout, contract status, and first-team playing time in high-level soccer players aged eight to eighteen years. J Strength Cond Res 2015; 29: 1692-1704
• 95 Zigova T, Pencea V, Wiegand SJ. et al. Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Mol Cell Neurosci 1998; 11: 234-245
• 96 McAllister AK, Katz LC, Lo DC. Neurotrophins and synaptic plasticity. Annu Rev Neurosci 1999; 22: 295-318
• 97 Egan MF, Kojima M, Callicott JH. et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003; 112: 257-269
• 98 Charlier R, Caspers M, Knaeps S. et al. Limited potential of genetic predisposition scores to predict muscle mass and strength performance in Flemish Caucasians between 19 and 73 years of age. Physiol Genomics 2017; 49: 160-166
• 99 Dong B, Li Q, Zhang T. et al. Population genetic polymorphism of skeletal muscle strength related genes in five ethnic minorities in North China. Front Genet 2021; 12: 756802
• 100 He L, Khanal P, Morse CI. et al. Associations of combined genetic and epigenetic scores with muscle size and muscle strength: a pilot study in older women. J Cachexia Sarcopenia Muscle 2020; 11: 1548-1561
• 101 He L, Van Roie E, Bogaerts A. et al. Genetic predisposition score predicts the increases of knee strength and muscle mass after one-year exercise in healthy elderly. Exp Gerontol 2018; 111: 17-26
• 102 Maciejewska-Skrendo A, Leźnicka K, Leońska-Duniec A. et al. Genetics of muscle stiffness, muscle elasticity and explosive strength. J Hum Kinet 2020; 74: 143-159
• 103 Brownlee TE. An investigation into the capabilities and affecting factors of isometric mid-thigh pull force production in elite youth soccer players. [Doctoral Thesis]: Liverpool John Moores University 2016;
• 104 Baumert P, Stewart CE, Lake MJ. et al. Variations of collagen-encoding genes are associated with exercise-induced muscle damage. Physiol Genomics 2018; 50: 691-693
• 105 Erskine RM, Williams AG, Jones DA. et al. Do PTK2 gene polymorphisms contribute to the interindividual variability in muscle strength and the response to resistance training? A preliminary report. J Appl Physiol (1985) 2012; 112: 1329-1334
• 106 Massidda M, Eynon N, Bachis V. et al. Association between MCT1 A1470T polymorphism and fat-free mass in well-trained young soccer players. J Strength Cond Res 2016; 30: 1171-1176
• 107 Erskine RM, Fletcher G, Folland JP. The contribution of muscle hypertrophy to strength changes following resistance training. Eur J Appl Physiol 2014; 114: 1239-1249
• 108 Nuell S, Illera-Domínguez V, Carmona G. et al. Hamstring muscle volume as an indicator of sprint performance. J Strength Cond Res 2021; 35: 902-909
• 109 Boraita A, de la Rosa A, Heras ME. et al. Cardiovascular adaptation, functional capacity and angiotensin-converting enzyme I/D polymorphism in elite athletes. Rev Esp Cardiol 2010; 63: 810-819
• 110 Papadimitriou ID, Papadopoulos C, Kouvatsi A. et al. The ACTN3 gene in elite Greek track and field athletes. Int J Sports Med 2008; 29: 352-355
• 111 Pescatello LS, Kostek MA, Gordish-Dressman H. et al. ACE ID genotype and the muscle strength and size response to unilateral resistance training. Med Sci Sports Exerc 2006; 38: 1074-1081
• 112 Delecluse C. Influence of strength training on sprint running performance. Current findings and implications for training. Sports Med 1997; 24: 147-156
• 113 Dubouchaud H, Butterfield GE, Wolfel EE. et al. Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle. Am J Physiol Endocrinol Metab 2000; 278: E571-E579
• 114 Stafilidis S, Arampatzis A. Muscle-tendon unit mechanical and morphological properties and sprint performance. J Sports Sci 2007; 25: 1035-1046
• 115 Morin JB, Gimenez P, Edouard P. et al. Sprint acceleration mechanics: The major role of hamstrings in horizontal force production. Front Physiol 2015; 6: 404
• 116 Ding X, Jin Y, Wu Y. et al. Localization and cellular distribution of CPNE5 in embryonic mouse brain. Brain Res 2008; 1224: 20-28
• 117 Reiner A, Yang M, Cagle MC. et al. Localization of cerebellin-2 in late embryonic chicken brain: implications for a role in synapse formation and for brain evolution. J Comp Neurol 2011; 519: 2225-2251
• 118 Fernandez T, Morgan T, Davis N. et al. Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome. Am J Hum Genet 2004; 74: 1286-1293
• 119 Stølen T, Chamari K, Castagna C. et al. Physiology of soccer: an update. Sports Med 2005; 35: 501-536
• 120 Bueno S, Pasqua LA, de Araújo G. et al. The association of ACE genotypes on cardiorespiratory variables related to physical fitness in healthy men. PLoS One 2016; 11: e0165310
• 121 Konopka MJ, van den Bunder J, Rietjens G. et al. Genetics of long-distance runners and road cyclists–A systematic review with meta-analysis. Scand J Med Sci Sports 2022; 32: 1414-1429
• 122 Papadimitriou ID, Lockey SJ, Voisin S. et al. No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes. BMC Genomics 2018; 19: 13
• 123 Mirwald RL, Baxter-Jones AD, Bailey DA. et al. An assessment of maturity from anthropometric measurements. Med Sci Sports Exerc 2002; 34: 689-694
• 124 Casamichana D, Castellano J, Castagna C. Comparing the physical demands of friendly matches and small-sided games in semiprofessional soccer players. J Strength Cond Res 2012; 26: 837-843
• 125 Pickering C, Kiely J, Suraci B. et al. The magnitude of Yo-Yo test improvements following an aerobic training intervention are associated with total genotype score. PLoS One 2018; 13: e0207597
• 126 Parry L, Drust B. Is injury the major cause of elite soccer players being unavailable to train and play during the competitive season?. Phys Ther Sport 2006; 7: 58-64
• 127 Eirale C, Tol JL, Farooq A. et al. Low injury rate strongly correlates with team success in Qatari professional football. Br J Sports Med 2013; 47: 807-808
• 128 Carling C, Le Gall F, McCall A. et al. Squad management, injury and match performance in a professional soccer team over a championship-winning season. Eur J Sport Sci 2015; 15: 573-582
• 129 Larruskain J, Lekue JA, Diaz N. et al. A comparison of injuries in elite male and female football players: A five-season prospective study. Scand J Med Sci Sports 2018; 28: 237-245
• 130 Varley I, Patel S, Williams AG. et al. The current use, and opinions of elite athletes and support staff in relation to genetic testing in elite sport within the UK. Biol Sport 2018; 35: 13-19
• 131 Tucker AM. Common soccer injuries. Diagnosis, treatment and rehabilitation. Sports Med 1997; 23: 21-32
• 132 Laguette MJ, Abrahams Y, Prince S. et al. Sequence variants within the 3'-UTR of the COL5A1 gene alters mRNA stability: implications for musculoskeletal soft tissue injuries. Matrix Biol 2011; 30: 338-345
• 133 Posthumus M, September AV, Keegan M. et al. Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant. Br J Sports Med 2009; 43: 352-356
• 134 Posthumus M, September AV, O'Cuinneagain D. et al. The COL5A1 gene is associated with increased risk of anterior cruciate ligament ruptures in female participants. Am J Sports Med 2009; 37: 2234-2240
• 135 September AV, Cook J, Handley CJ. et al. Variants within the COL5A1 gene are associated with Achilles tendinopathy in two populations. Br J Sports Med 2009; 43: 357-365
• 136 Ahmetov II, Hall ECR, Semenova EA. et al. Advances in sports genomics. Adv Clin Chem 2022; 107: 215-263
• 137 Broos S, Malisoux L, Theisen D. et al. Evidence for ACTN3 as a speed gene in isolated human muscle fibers. PLoS One 2016; 11: e0150594
• 138 Timmins RG, Bourne MN, Shield AJ. et al. Short biceps femoris fascicles and eccentric knee flexor weakness increase the risk of hamstring injury in elite football (soccer): a prospective cohort study. Br J Sports Med 2016; 50: 1524-1535
• 139 Pimenta EM, Coelho DB, Cruz IR. et al. The ACTN3 genotype in soccer players in response to acute eccentric training. Eur J Appl Physiol 2012; 112: 1495-1503
• 140 Clos E, Pruna R, Lundblad M. et al. ACTN3 single nucleotide polymorphism is associated with non-contact musculoskeletal soft-tissue injury incidence in elite professional football players. Knee Surg Sports Traumatol Arthrosc 2019; 27: 4055-4061
• 141 Bradley PS, Dellal A, Mohr M. et al. Gender differences in match performance characteristics of soccer players competing in the UEFA Champions League. Hum Mov Sci 2014; 33: 159-171
• 142 Waldén M, Hägglund M, Werner J. et al. The epidemiology of anterior cruciate ligament injury in football (soccer): a review of the literature from a gender-related perspective. Knee Surg Sports Traumatol Arthrosc 2011; 19: 3-10
• 143 Del Coso J, Rodas G, Buil M. et al. Association of the ACTN3 rs1815739 polymorphism with physical performance and injury incidence in professional women football players. Genes (Basel) 2022; 13: 1635
• 144 Baumert P, Lake MJ, Stewart CE. et al. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. Eur J Appl Physiol 2016; 116: 1595-1625
• 145 Mann V, Hobson EE, Li B. et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107: 899-907
• 146 Boot-Handford RP, Tuckwell DS. Fibrillar collagen: the key to vertebrate evolution? A tale of molecular incest. Bioessays 2003; 25: 142-151
• 147 Posthumus M, September AV, Schwellnus MP. et al. Investigation of the Sp1-binding site polymorphism within the COL1A1 gene in participants with Achilles tendon injuries and controls. J Sci Med Sport 2009; 12: 184-189
• 148 Jin H, van't Hof RJ, Albagha OM. et al. Promoter and intron 1 polymorphisms of COL1A1 interact to regulate transcription and susceptibility to osteoporosis. Hum Mol Genet 2009; 18: 2729-2738
• 149 Collins M, Posthumus M. Type V collagen genotype and exercise-related phenotype relationships: a novel hypothesis. Exerc Sport Sci Rev 2011; 39: 191-198
• 150 Wenstrup RJ, Florer JB, Brunskill EW. et al. Type V collagen controls the initiation of collagen fibril assembly. J Biol Chem 2004; 279: 53331-53337
• 151 Zacchigna L, Vecchione C, Notte A. et al. Emilin1 links TGF-beta maturation to blood pressure homeostasis. Cell 2006; 124: 929-942
• 152 Randell A, Daneshtalab N. Elastin microfibril interface-located protein 1, transforming growth factor beta, and implications on cardiovascular complications. J Am Soc Hypertens 2017; 11: 437-448
• 153 Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports 2000; 10: 312-320
• 154 Posthumus M, Collins M, van der Merwe L. et al. Matrix metalloproteinase genes on chromosome 11q22 and the risk of anterior cruciate ligament (ACL) rupture. Scand J Med Sci Sports 2012; 22: 523-533
• 155 Birkedal-Hansen H, Moore WG, Bodden MK. et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 1993; 4: 197-250
• 156 Chen X, Li Y. Role of matrix metalloproteinases in skeletal muscle: migration, differentiation, regeneration and fibrosis. Cell Adh Migr 2009; 3: 337-341
• 157 Medley TL, Kingwell BA, Gatzka CD. et al. Matrix metalloproteinase-3 genotype contributes to age-related aortic stiffening through modulation of gene and protein expression. Circ Res 2003; 92: 1254-1261
• 158 Guo YQ, Zheng LN, Wei JF. et al. Expression of CCL2 and CCR2 in the hippocampus and the interventional roles of propofol in rat cerebral ischemia/reperfusion. Exp Ther Med 2014; 8: 657-661
• 159 Hubal MJ, Chen TC, Thompson PD. et al. Inflammatory gene changes associated with the repeated-bout effect. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1628-R1637
• 160 Catoire M, Kersten S. The search for exercise factors in humans. FASEB J 2015; 29: 1615-1628
• 161 Hubal MJ, Devaney JM, Hoffman EP. et al. CCL2 and CCR2 polymorphisms are associated with markers of exercise-induced skeletal muscle damage. J Appl Physiol (1985) 2010; 108: 1651-1658
• 162 Yahiaoui L, Gvozdic D, Danialou G. et al. CC family chemokines directly regulate myoblast responses to skeletal muscle injury. J Physiol 2008; 586: 3991-4004
• 163 Fishman D, Faulds G, Jeffery R. et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 1998; 102: 1369-1376
• 164 Andersen MB, Pingel J, Kjær M. et al. Interleukin-6: a growth factor stimulating collagen synthesis in human tendon. J Appl Physiol (1985) 2011; 110: 1549-1554
• 165 Muñoz-Cánoves P, Scheele C, Pedersen BK. et al. Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword?. FEBS J 2013; 280: 4131-4148
• 166 Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008; 88: 1379-1406
• 167 Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR. et al. Influence of mode and carbohydrate on the cytokine response to heavy exertion. Med Sci Sports Exerc 1998; 30: 671-678
• 168 Millar NL, Wei AQ, Molloy TJ. et al. Cytokines and apoptosis in supraspinatus tendinopathy. J Bone Joint Surg Br 2009; 91: 417-424
• 169 Yamin C, Duarte JA, Oliveira JM. et al. IL6 (-174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise. Eur J Appl Physiol 2008; 104: 579-586
• 170 Massidda M, Eynon N, Bachis V. et al. Influence of the MCT1 rs1049434 on indirect muscle disorders/injuries in elite football players. Sports Med Open 2015; 1: 33
• 171 Massidda M, Corrias L, Bachis V. et al. Vitamin D receptor gene polymorphisms and musculoskeletal injuries in professional football players. Exp Ther Med 2015; 9: 1974-1978
• 172 Bouchard C. Overcoming barriers to progress in exercise genomics. Exerc Sport Sci Rev 2011; 39: 212-217
• 173 Mills M, Yang N, Weinberger R. et al. 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 2001; 10: 1335-1346
• 174 Reneland R, Lithell H. Angiotensin-converting enzyme in human skeletal muscle. A simple in vitro assay of activity in needle biopsy specimens. Scand J Clin Lab Invest 1994; 54: 105-111
• 175 Gordon SE, Davis BS, Carlson CJ. et al. ANG II is required for optimal overload-induced skeletal muscle hypertrophy. Am J Physiol Endocrinol Metab 2001; 280: E150-E159
• 176 Rigat B, Hubert C, Alhenc-Gelas F. et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343-1346
• 177 Charbonneau DE, Hanson ED, Ludlow AT. et al. ACE genotype and the muscle hypertrophic and strength responses to strength training. Med Sci Sports Exerc 2008; 40: 677-683
• 178 North KN, Beggs AH. Deficiency of a skeletal muscle isoform of alpha-actinin (alpha-actinin-3) in merosin-positive congenital muscular dystrophy. Neuromuscul Disord 1996; 6: 229-235
• 179 Sethi AA, Nordestgaard BG, Tybjaerg-Hansen A. Angiotensinogen gene polymorphism, plasma angiotensinogen, and risk of hypertension and ischemic heart disease: a meta-analysis. Arterioscler Thromb Vasc Biol 2003; 23: 1269-1275
• 180 Morisaki T, Gross M, Morisaki H. et al. Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci U S A 1992; 89: 6457-6461
• 181 Kuntz LA, Rossetti L, Kunold E. et al. Biomarkers for tissue engineering of the tendon-bone interface. PLoS One 2018; 13: e0189668
• 182 Birk DE, Fitch JM, Babiarz JP. et al. Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. J Cell Sci 1990; 95: 649-657
• 183 Halestrap AP, Meredith D. The SLC16 gene family–from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 2004; 447: 619-628
• 184 Massidda M, Flore L, Kikuchi N. et al. Influence of the MCT1-T1470A polymorphism (rs1049434) on repeated sprint ability and blood lactate accumulation in elite football players: a pilot study. Eur J Appl Physiol 2021; 121: 3399-3408
• 185 Nakayama M, Yasue H, Yoshimura M. et al. T(-786)-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis. Am J Cardiol 2000; 86: 628-634
• 186 Kersten S. Integrated physiology and systems biology of PPARα. Mol Metab 2014; 3: 354-371
• 187 Ahmetov II, Mozhayskaya IA, Flavell DM. et al. PPARalpha gene variation and physical performance in Russian athletes. Eur J Appl Physiol 2006; 97: 103-108
• 188 Auton A, Brooks LD, Durbin RM. et al. A global reference for human genetic variation. Nature 2015; 526: 68-74
• 189 McKee TJ, Perlman G, Morris M. et al. Extracellular matrix composition of connective tissues: a systematic review and meta-analysis. Sci Rep 2019; 9: 10542
• 190 Oh VM, Chua BM, Heng CK. et al. Association of intronic single-nucleotide polymorphisms in the EMILIN1 gene with essential hypertension in a Chinese population. J Hum Hypertens 2012; 26: 553-561
• 191 Nie G, Wen X, Liang X. et al. Additional evidence supports association of common genetic variants in MMP3 and TIMP2 with increased risk of chronic Achilles tendinopathy susceptibility. J Sci Med Sport 2019; 22: 1074-1078