Single Nucleotide Polymorphisms and Tendon/Ligament Injuries in Athletes: A Systematic Review and Meta-analysis

Abstract

This systematic review and meta-analysis aimed to identify the association between genetic polymorphisms and tendon and ligament injuries in adolescent and adult athletes of multiple competition sports. The PubMed, Web of Science, EBSCO, Cochrane Library, and MEDLINE databases were searched until July 7, 2023. Eligible articles included genetic studies on tendon and ligament injuries and comparisons between injured and non-injured athletes. This review included 31 articles, comprising 1,687 injury cases and 2,227 controls, from a meta-analysis of 12 articles. We identified 144 candidate gene polymorphisms (only single nucleotide polymorphisms were identified). The meta-analyses included vascular endothelial growth factor A (VEGFA) rs699947, collagen type I alpha 1 rs1800012, collagen type V alpha 1 rs12722, and matrix metalloproteinase 3 rs679620. The VEGFA rs699947 polymorphism showed a lower risk of injuries in athletes with the C allele ([C vs. A]: OR=0.80, 95% CI: 0.65–0.98, I ² =3.82%, p=0.03). The risk of these injuries were not affected by other polymorphisms. In conclusion, the VEGFA rs699947 polymorphism is associated with the risk of tendon and ligament injuries in athletes. This study provides insights into genetic variations that contribute to our understanding of the risk factors for such injuries in athletes.

Keywords

genetic factor - genetic polymorphism - sports injury

Publication History

Received: 30 April 2024

Accepted: 05 September 2024

Article published online:
22 October 2024

• References

• 1 Clifton DR, Hertel J, Onate JA. et al. The First Decade of Web-Based Sports Injury Surveillance: Descriptive Epidemiology of Injuries in US High School Girlsʼ Basketball (2005–2006 Through 2013–2014) and National Collegiate Athletic Association Womenʼs Basketball (2004–2005 Through 2013–2014). J Athl Train 2018; 53: 1037-1048
• 2 Lai CCH, Ardern CL, Feller JA. et al. Eighty-three per cent of elite athletes return to preinjury sport after anterior cruciate ligament reconstruction: A systematic review with meta-analysis of return to sport rates, graft rupture rates and performance outcomes. Br J Sports Med 2018; 52: 128-138
• 3 Forlenza EM, Lavoie-Gagne OZ, Lu Y. et al. Return to Play and Player Performance After Achilles Tendon Rupture in UEFA Professional Soccer Players: A Matched-Cohort Analysis of Players From 1999 to 2018. Orthop J Sports Med 2021; 9 23259671211024199
• 4 Ardern CL, Taylor NF, Feller JA. et al. Fifty-five per cent return to competitive sport following anterior cruciate ligament reconstruction surgery: An updated systematic review and meta-analysis including aspects of physical functioning and contextual factors. Br J Sports Med 2014; 48: 1543-1552
• 5 Webster KE, Feller JA. Expectations for Return to Preinjury Sport Before and After Anterior Cruciate Ligament Reconstruction. Am J Sports Med 2019; 47: 578-583
• 6 Lavoie-Gagne OZ, Retzky J, Diaz CC. et al. Return-to-Play Times and Player Performance After Medial Collateral Ligament Injury in Elite-Level European Soccer Players. Orthop J Sports Med 2021; 9 23259671211033904
• 7 Chauhan A, Stotts J, Ayeni OR. et al. Return to play, performance, and value of National Basketball Association players following Achilles tendon rupture. Phys Sportsmed 2021; 49: 271-277
• 8 Zbrojkiewicz D, Vertullo C, Grayson JE. Increasing rates of anterior cruciate ligament reconstruction in young Australians, 2000–2015. Med J Aust 2018; 208: 354-358
• 9 Herzog MM, Marshall SW, Lund JL. et al. Trends in Incidence of ACL Reconstruction and Concomitant Procedures Among Commercially Insured Individuals in the United States, 2002–2014. Sports Health 2018; 10: 523-531
• 10 Lemme NJ, Li NY, DeFroda SF. et al. Epidemiology of Achilles Tendon Ruptures in the United States: Athletic and Nonathletic Injuries From 2012 to 2016. Orthop J Sports Med 2018; 6 2325967118808238
• 11 Duthon VB, Barea C, Abrassart S. et al. Anatomy of the anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc 2006; 14: 204-213
• 12 Frank CB. Ligament structure, physiology and function. J Musculoskelet Neuronal Interact 2004; 4: 199-201
• 13 Niyibizi C, Kavalkovich K, Yamaji T. et al. Type V collagen is increased during rabbit medial collateral ligament healing. Knee Surg Sports Traumatol Arthrosc 2000; 8: 281-285
• 14 Magnusson SP, Qvortrup K, Larsen JO. et al. Collagen fibril size and crimp morphology in ruptured and intact Achilles tendons. Matrix Biol 2002; 21: 369-377
• 15 Font B, Eichenberger D, Rosenberg LM. et al. Characterization of the interactions of type XII collagen with two small proteoglycans from fetal bovine tendon, decorin and fibromodulin. Matrix Biol 1996; 15: 341-348
• 16 Kjaer M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 2004; 84: 649-698
• 17 Zhang G, Ezura Y, Chervoneva I. et al. Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development. J Cell Biochem 2006; 98: 1436-1449
• 18 Nastase MV, Young MF, Schaefer L. Biglycan: A multivalent proteoglycan providing structure and signals. J Histochem Cytochem 2012; 60: 963-975
• 19 Beach ZM, Bonilla KA, Dekhne MS. et al. Biglycan has a major role in maintenance of mature tendon mechanics. J Orthop Res 2022; 40: 2546-2556
• 20 Thorpe CT, Birch HL, Clegg PD. et al. The role of the non-collagenous matrix in tendon function. Int J Exp Pathol 2013; 94: 248-259
• 21 Järvinen TA, Józsa L, Kannus P. et al. Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle. J Cell Sci 2003; 116: 857-866
• 22 Stamenkovic I. Extracellular matrix remodelling: The role of matrix metalloproteinases. J Pathol 2003; 200: 448-464
• 23 Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92: 827-839
• 24 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
• 25 Khoschnau S, Melhus H, Jacobson A. et al. Type I collagen alpha1 Sp1 polymorphism and the risk of cruciate ligament ruptures or shoulder dislocations. Am J Sports Med 2008; 36: 2432-2436
• 26 OʼConnell K, Knight H, Ficek K. et al. Interactions between collagen gene variants and risk of anterior cruciate ligament rupture. Eur J Sport Sci 2015; 15: 341-350
• 27 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
• 28 Rahim M, Gibbon A, Hobbs H. et al. The association of genes involved in the angiogenesis-associated signaling pathway with risk of anterior cruciate ligament rupture. J Orthop Res 2014; 32: 1612-1618
• 29 Flynn RK, Pedersen CL, Birmingham TB. et al. The familial predisposition toward tearing the anterior cruciate ligament: A case control study. Am J Sports Med 2005; 33: 23-28
• 30 Westin M, Reeds-Lundqvist S, Werner S. The correlation between anterior cruciate ligament injury in elite alpine skiers and their parents. Knee Surg Sports Traumatol Arthrosc 2016; 24: 697-701
• 31 Liberati A, Altman DG, Tetzlaff J. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. Bmj 2009; 339: b2700
• 32 Wells GASB, OʼConnell D, Peterson J. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, Ontario: Ottawa Health Research Institute, University of Ottawa: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
• 33 Shukla M, Gupta R, Pandey V. et al. COLIA1+1245 G>T Sp1 Binding Site Polymorphism is Not Associated with ACL Injury Risks Among Indian Athletes. Indian J Orthop 2020; 54: 647-654
• 34 Rodas G, Cáceres A, Ferrer E. et al. Sex Differences in the Association between Risk of Anterior Cruciate Ligament Rupture and COL5A1 Polymorphisms in Elite Footballers. Genes 2023; 14: 33
• 35 Miyamoto-Mikami E, Zempo H, Fuku N. et al. Heritability estimates of endurance-related phenotypes: A systematic review and meta-analysis. Scand J Med Sci Sports 2018; 28: 834-845
• 36 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
• 37 Cięszczyk P, Willard K, Gronek P. et al. Are genes encoding proteoglycans really associated with the risk of anterior cruciate ligament rupture?. Biol Sport 2017; 34: 97-103
• 38 Ficek K, Stepien-Slodkowska M, Kaczmarczyk M. et al. Does the A9285G Polymorphism in Collagen Type XII α1 Gene Associate with the Risk of Anterior Cruciate Ligament Ruptures?. Balkan J Med Genet 2014; 17: 41-46
• 39 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
• 40 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
• 41 Lulińska-Kuklik E, Leźnicka K, Humińska-Lisowska K. et al. The VEGFA gene and anterior cruciate ligament rupture risk in the Caucasian population. Biol Sport 2019; 36: 3-8
• 42 Lulińska-Kuklik E, Laguette MN, Moska W. et al. Are TNC gene variants associated with anterior cruciate ligament rupture susceptibility?. J Sci Med Sport 2019; 22: 408-412
• 43 Lulińska-Kuklik E, Rahim M, Moska W. et al. Are MMP3, MMP8 and TIMP2 gene variants associated with anterior cruciate ligament rupture susceptibility?. J Sci Med Sport 2019; 22: 753-757
• 44 Lulińska-Kuklik E, Maculewicz E, Moska W. et al. Are IL1B, IL6 and IL6R Gene Variants Associated with Anterior Cruciate Ligament Rupture Susceptibility?. J Sports Sci Med 2019; 18: 137-145
• 45 Lulińska E, Gibbon A, Kaczmarczyk M. et al. Matrix Metalloproteinase Genes (MMP1, MMP10, MMP12) on Chromosome 11q22 and the Risk of Non-Contact Anterior Cruciate Ligament Ruptures. Genes (Basel) 2020; 11
• 46 LuliŃSka E, ŻElazny J, LuliŃSka A. et al. Genetic variants and anterior cruciate ligament rupture – Elastin proteins gene and fibromodulin gene polymorphisms. Balt J Health Phys Act 2023; 15: 1-11
• 47 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
• 48 Pruna R, Ribas J, Montoro JB. et al. The impact of single nucleotide polymorphisms on patterns of non-contact musculoskeletal soft tissue injuries in a football player population according to ethnicity. Med Clin (Barc). 2015. 144. 105-110
• 49 Sun Z, Cieszczyk P, Lulinska E. et al. Are COL22A1 Gene Polymorphisms rs11784270 and rs6577958 Associated with Susceptibility to a Non-Contact Anterior Cruciate Ligament Injury in Polish Athletes?. Int J Environ Res Public Health 2022; 20
• 50 Salles JI, Amaral MV, Aguiar DP. et al. BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes. J Sci Med Sport 2015; 18: 150-155
• 51 Salles JI, Duarte ME, Guimarães JM. et al. Vascular Endothelial Growth Factor Receptor-2 Polymorphisms Have Protective Effect against the Development of Tendinopathy in Volleyball Athletes. PLoS One 2016; 11: e0167717
• 52 Salles JI, Lopes LR, Duarte MEL. et al. Fc receptor-like 3 (-169T>C) polymorphism increases the risk of tendinopathy in volleyball athletes: A case control study. BMC Med Genet 2018; 19: 119
• 53 Gutiérrez-Hellín J, Baltazar-Martins G, Aguilar-Navarro M. et al. Effect of ACTN3 R577X Genotype on Injury Epidemiology in Elite Endurance Runners. Genes (Basel) 2021; 12
• 54 Jacob Y, Anderton RS, Wilkie JLC. et al. Genetic Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian Football League Players: A Preliminary Study. Sports Med Open 2022; 8
• 55 Alakhdar Y, Cook J, Gallego D. et al. Association Between COL5a1, COL11a1, and COL11a2 Gene Variations and Rotator Cuff Tendinopathy in Young Athletes. Clin J Sport Med 2023;
• 56 Briški N, Vrgoč G, Knjaz D. et al. Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: Case-control study in high-level athletes. Int Orthop 2021; 45: 1163-1168
• 57 Lopes LR, de Miranda VAR, Guimarães JAM. et al. Association of TNF-α -308G>A polymorphism with susceptibility to tendinopathy in athletes: A case-control study. BMC Sports Sci Med Rehabil 2021; 13: 51
• 58 Lopes LR, Guimarães JAM, Amaral MVG. et al. Genetic Polymorphisms in COL1A2 gene and the Risk of Tendinopathy: Case-Control Study. Rev Bras Ortop 2023; 58: 478-486
• 59 Mirghaderi SP, Salimi M, Kheirollahi M. et al. Anterior cruciate ligament injury and its postoperative outcomes are not associated with polymorphism in COL1A1 rs1107946 (G/T): A case-control study in the Middle East elite athletes. J Orthop Surg Res 2022; 17: 462
• 60 Perini JA, Lopes LR, Guimarães JAM. et al. Influence of type I collagen polymorphisms and risk of anterior cruciate ligament rupture in athletes: A case-control study. BMC Musculoskelet Disord 2022; 23: 154
• 61 Rodas G, Osaba L, Arteta D. et al. Genomic Prediction of Tendinopathy Risk in Elite Team Sports. Int J Sports Physiol Perform 2019; 15: 489-495
• 62 Shukla M, Gupta R, Pandey V. et al. VEGFA Promoter Polymorphisms rs699947 and rs35569394 Are Associated With the Risk of Anterior Cruciate Ligament Ruptures Among Indian Athletes: A Cross-sectional Study. Orthop J Sports Med 2020; 8: 2325967120964472
• 63 Sivertsen EA, Haug KBF, Kristianslund EK. et al. No Association Between Risk of Anterior Cruciate Ligament Rupture and Selected Candidate Collagen Gene Variants in Female Elite Athletes From High-Risk Team Sports. Am J Sports Med 2019; 47: 52-58
• 64 Kannus P. Structure of the tendon connective tissue. Scand J Med Sci Sports 2000; 10: 312-320
• 65 Junien C, Weil D, Myers JC. et al. Assignment of the human pro alpha 2(I) collagen structural gene (COLIA2) to chromosome 7 by molecular hybridization. Am J Hum Genet 1982; 34: 381-387
• 66 Gelse K, Pöschl E, Aigner T. Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev 2003; 55: 1531-1546
• 67 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
• 68 Wang C, Li H, Chen K. et al. Association of polymorphisms rs1800012 in COL1A1 with sports-related tendon and ligament injuries: A meta-analysis. Oncotarget 2017; 8: 27627-27634
• 69 Cameron GJ, Alberts IL, Laing JH. et al. Structure of type I and type III heterotypic collagen fibrils: An X-ray diffraction study. J Struct Biol 2002; 137: 15-22
• 70 Kuivaniemi H, Tromp G. Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases. Gene 2019; 707: 151-171
• 71 Ireland D, Harrall R, Curry V. et al. Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol 2001; 20: 159-169
• 72 Chen HY, Chung YW, Lin WY. et al. Collagen type 3 alpha 1 polymorphism and risk of pelvic organ prolapse. Int J Gynaecol Obstet 2008; 103: 55-58
• 73 Kluivers KB, Dijkstra JR, Hendriks JC. et al. COL3A1 2209G>A is a predictor of pelvic organ prolapse. Int Urogynecol J Pelvic Floor Dysfunct 2009; 20: 1113-1118
• 74 Stępień-Słodkowska M, Ficek K, Maciejewska-Karłowska A. et al. Overrepresentation of the COL3A1 AA genotype in Polish skiers with anterior cruciate ligament injury. Biol Sport 2015; 32: 143-147
• 75 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
• 76 Wenstrup RJ, Florer JB, Davidson JM. et al. Murine model of the Ehlers-Danlos syndrome. col5a1 haploinsufficiency disrupts collagen fibril assembly at multiple stages. J Biol Chem 2006; 281: 12888-12895
• 77 Young BB, Zhang G, Koch M. et al. The roles of types XII and XIV collagen in fibrillogenesis and matrix assembly in the developing cornea. J Cell Biochem 2002; 87: 208-220
• 78 Cui N, Hu M, Khalil RA. Biochemical and Biological Attributes of Matrix Metalloproteinases. Prog Mol Biol Transl Sci 2017; 147: 1-73
• 79 Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 2007; 8: 221-233
• 80 Laronha H, Caldeira J. Structure and Function of Human Matrix Metalloproteinases. Cells 2020; 9
• 81 Alameddine HS, Morgan JE. Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Inflammation and Fibrosis of Skeletal Muscles. J Neuromuscul Dis 2016; 3: 455-473
• 82 Klatte-Schulz F, Minkwitz S, Schmock A. et al. Different Achilles Tendon Pathologies Show Distinct Histological and Molecular Characteristics. Int J Mol Sci 2018; 19
• 83 Dalton S, Cawston TE, Riley GP. et al. Human shoulder tendon biopsy samples in organ culture produce procollagenase and tissue inhibitor of metalloproteinases. Ann Rheum Dis 1995; 54: 571-577
• 84 Karousou E, Ronga M, Vigetti D. et al. Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture. Clin Orthop Relat Res 2008; 466: 1577-1582
• 85 Leong NL, Kator JL, Clemens TL. et al. Tendon and Ligament Healing and Current Approaches to Tendon and Ligament Regeneration. J Orthop Res 2020; 38: 7-12
• 86 Marui T, Niyibizi C, Georgescu HI. et al. Effect of growth factors on matrix synthesis by ligament fibroblasts. J Orthop Res 1997; 15: 18-23
• 87 Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med 2003; 33: 381-394
• 88 Tang C, Chen Y, Huang J. et al. The roles of inflammatory mediators and immunocytes in tendinopathy. J Orthop Translat 2018; 14: 23-33
• 89 Chen Y, Tai Z, Zhu C. et al. Vascular Endothelial Growth Factor A VEGFA Inhibition: An Effective Treatment Strategy for Psoriasis. Int J Mol Sci 2023; 25
• 90 Pufe T, Kurz B, Petersen W. et al. The influence of biomechanical parameters on the expression of VEGF and endostatin in the bone and joint system. Ann Anat 2005; 187: 461-472
• 91 Sato Y, Abe M, Tanaka K. et al. Signal transduction and transcriptional regulation of angiogenesis. Adv Exp Med Biol 2000; 476: 109-115
• 92 Qi JH, Ebrahem Q, Moore N. et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): Inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med 2003; 9: 407-415
• 93 Pufe T, Petersen WJ, Mentlein R. et al. The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease. Scand J Med Sci Sports 2005; 15: 211-222
• 94 Chisari E, Rehak L, Khan WS. et al. Tendon healing is adversely affected by low-grade inflammation. J Orthop Surg Res 2021; 16: 700
• 95 Riley GP, Curry V, DeGroot J. et al. Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol 2002; 21: 185-195
• 96 Shahbazi M, Fryer AA, Pravica V. et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol 2002; 13: 260-264
• 97 Awata T, Kurihara S, Takata N. et al. Functional VEGF C-634G polymorphism is associated with development of diabetic macular edema and correlated with macular retinal thickness in type 2 diabetes. Biochem Biophys Res Commun 2005; 333: 679-685
• 98 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
• 99 Li J, Jiang L, Zhou X. et al. The association between Interleukin-6 rs1800795/rs1800797 polymorphisms and risk of rotator cuff tear in a Chinese population. Biosci Rep 2020; 40
• 100 Cole SW, Arevalo JM, Takahashi R. et al. Computational identification of gene-social environment interaction at the human IL6 locus. Proc Natl Acad Sci U S A 2010; 107: 5681-5686
• 101 Cohen T, Nahari D, Cerem LW. et al. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 1996; 271: 736-741
• 102 Rahim M, Mannion S, Klug B. et al. Modulators of the extracellular matrix and risk of anterior cruciate ligament ruptures. J Sci Med Sport 2017; 20: 152-158
• 103 Rahim M, Lacerda M, Collins M. et al. Risk modelling further implicates the angiogenesis pathway in anterior cruciate ligament ruptures. Eur J Sport Sci 2022; 22: 650-657
• 104 Kirkendall DT, Garrett WE. Function and biomechanics of tendons. Scand J Med Sci Sports 1997; 7: 62-66
• 105 Gosline J, Lillie M, Carrington E. et al. Elastic proteins: Biological roles and mechanical properties. Philos Trans R Soc Lond B Biol Sci 2002; 357: 121-132
• 106 Muiznieks LD, Weiss AS, Keeley FW. Structural disorder and dynamics of elastin. Biochem Cell Biol 2010; 88: 239-250
• 107 Giudici A, Wilkinson IB, Khir AW. Review of the Techniques Used for Investigating the Role Elastin and Collagen Play in Arterial Wall Mechanics. IEEE Rev Biomed Eng 2021; 14: 256-269
• 108 Yoon JH, Halper J. Tendon proteoglycans: Biochemistry and function. J Musculoskelet Neuronal Interact 2005; 5: 22-34
• 109 Reed CC, Iozzo RV. The role of decorin in collagen fibrillogenesis and skin homeostasis. Glycoconj J 2002; 19: 249-255
• 110 Järvinen TA, Kannus P, Järvinen TL. et al. Tenascin-C in the pathobiology and healing process of musculoskeletal tissue injury. Scand J Med Sci Sports 2000; 10: 376-382
• 111 Tabor HK, Risch NJ, Myers RM. Candidate-gene approaches for studying complex genetic traits: Practical considerations. Nat Rev Genet 2002; 3: 391-397
• 112 Willard K, Laguette MN, Alves de Souza Rios L. et al. Altered expression of proteoglycan, collagen and growth factor genes in a TGF-β1 stimulated genetic risk model for musculoskeletal soft tissue injuries. J Sci Med Sport 2020; 23: 695-700