Genetic Aspects in Shoulder Disorders^[∗]

Abstract

The influence of genetic inheritance has been increasingly investigated in shoulder disorders, such as rotator cuff injury, instability and frozen shoulder. Although the initial findings are enlightening, it is necessary to progressively build a database of genetic markers to catalog genomic profiles that, later, may contribute for predicting the risk of the disease, as well as to the development of better diagnostic and treatment tools. The present article seeks to update what is evidence of genetic studies in the literature for these diseases, from polymorphism analyses, expression of candidate genes in tissues and broad genomic association studies (GWAS). However, it is necessary to point out that there is great difficulty in replicating and using the findings, mainly due to the lack of statistical power, the high rate of false-positive results and the large number of variables involved.

Keywords

shoulder - genetic polymorphism - gene expression

^∗ Work developed in the Sports Medicine and Physical Activity Discipline, Sports Traumatology Center (CETE, in the Portuguese acronym), Universidade Federal de São Paulo (UNIFESP, in the Portuguese acronym), São Paulo, SP, Brazil.

Publikationsverlauf

Eingereicht: 05. September 2019

Angenommen: 12. November 2019

Artikel online veröffentlicht:
08. Juni 2020

• Referências

• 1 Lander ES, Linton LM, Birren B. et al. Initial sequencing and analysis of the human genome. Nature 2001; 409 (6822): 860-921
• 2 Leal MF, Belangero SI. Variantes genéticas nas lesões do sistema musculoesquelético em atletas. In: Cohen M, Abdalla RJ. Lesões nos Esportes: Diagnóstico, Prevenção e Tratamento. 2^a. ed. Rio de Janeiro: Revinter; 2015: 5-56
• 3 Frank CB. Ligament structure, physiology and function. J Musculoskelet Neuronal Interact 2004; 4 (02) 199-201
• 4 Mitchell AL, Schwarze U, Jennings JF, Byers PH. Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS). Hum Mutat 2009; 30 (06) 995-1002
• 5 Chiquet-Ehrismann R, Tucker RP. Tenascins and the importance of adhesion modulation. Cold Spring Harb Perspect Biol 2011; 3 (05) a004960
• 6 Dallas SL, Sivakumar P, Jones CJ. et al. Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. J Biol Chem 2005; 280 (19) 18871-18880
• 7 Badalamenti MA, Sampson SP, Hurst LC, Dowd A, Miyasaka K. The role of TGF-beta in Dupuytren's disease. J Hand Surg Am 1996; 21 (02) 210-215
• 8 Wahl SM, Costa GL, Mizel DE, Allen JB, Skaleric U, Mangan DF. Role of transforming growth factor beta in the pathophysiology of chronic inflammation. J Periodontol 1993; 64 (5, Suppl) 450-455
• 9 Ulrich D, Hrynyschyn K, Pallua N. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in sera and tissue of patients with Dupuytren's disease. Plast Reconstr Surg 2003; 112 (05) 1279-1286
• 10 Dabija DI, Gao C, Edwards TL, Kuhn JE, Jain NB. Genetic and familial predisposition to rotator cuff disease: a systematic review. J Shoulder Elbow Surg 2017; 26 (06) 1103-1112
• 11 Harvie P, Ostlere SJ, Teh J. et al. Genetic influences in the aetiology of tears of the rotator cuff. Sibling risk of a full-thickness tear. J Bone Joint Surg Br 2004; 86 (05) 696-700
• 12 Gwilym SE, Watkins B, Cooper CD. et al. Genetic influences in the progression of tears of the rotator cuff. J Bone Joint Surg Br 2009; 91 (07) 915-917
• 13 Tashjian RZ, Farnham JM, Albright FS, Teerlink CC, Cannon-Albright LA. Evidence for an inherited predisposition contributing to the risk for rotator cuff disease. J Bone Joint Surg Am 2009; 91 (05) 1136-1142
• 14 Tashjian RZ, Saltzman EG, Granger EK, Hung M. Incidence of familial tendon dysfunction in patients with full-thickness rotator cuff tears. Open Access J Sports Med 2014; 5: 137-141
• 15 Gumina S, Villani C, Arceri V. et al. Rotator Cuff Degeneration: The Role of Genetics. J Bone Joint Surg Am 2019; 101 (07) 600-605
• 16 Riley GP, Curry V, DeGroot J. et al. Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol 2002; 21 (02) 185-195
• 17 Lo IK, Boorman R, Marchuk L, Hollinshead R, Hart DA, Frank CB. Matrix molecule mRNA levels in the bursa and rotator cuff of patients with full-thickness rotator cuff tears. Arthroscopy 2005; 21 (06) 645-651
• 18 Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB. Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 2004; 32 (05) 1223-1229
• 19 Shindle MK, Chen CC, Robertson C. et al. Full-thickness supraspinatus tears are associated with more synovial inflammation and tissue degeneration than partial-thickness tears. J Shoulder Elbow Surg 2011; 20 (06) 917-927
• 20 Shirachi I, Gotoh M, Mitsui Y. et al. Collagen production at the edge of ruptured rotator cuff tendon is correlated with postoperative cuff integrity. Arthroscopy 2011; 27 (09) 1173-1179
• 21 Robertson CM, Chen CT, Shindle MK, Cordasco FA, Rodeo SA, Warren RF. Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons. Am J Sports Med 2012; 40 (09) 1993-2001
• 22 Gotoh M, Mitsui Y, Shibata H. et al. Increased matrix metalloprotease-3 gene expression in ruptured rotator cuff tendons is associated with postoperative tendon retear. Knee Surg Sports Traumatol Arthrosc 2013; 21 (08) 1807-1812
• 23 Motta GdaR, Amaral MV, Rezende E. et al. Evidence of genetic variations associated with rotator cuff disease. J Shoulder Elbow Surg 2014; 23 (02) 227-235
• 24 Teerlink CC, Cannon-Albright LA, Tashjian RZ. Significant association of full-thickness rotator cuff tears and estrogen-related receptor-β (ESRRB). J Shoulder Elbow Surg 2015; 24 (02) e31-e35 Erratum in: J Shoulder Elbow Surg 2016;25(5):864
• 25 Tashjian RZ, Granger EK, Farnham JM, Cannon-Albright LA, Teerlink CC. Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms. J Shoulder Elbow Surg 2016; 25 (02) 174-179
• 26 Assunção JH, Godoy-Santos AL, Dos Santos MCLG, Malavolta EA, Gracitelli MEC, Ferreira Neto AA. Matrix Metalloproteases 1 and 3 Promoter Gene Polymorphism Is Associated With Rotator Cuff Tear. Clin Orthop Relat Res 2017; 475 (07) 1904-1910
• 27 Sejersen MH, Frost P, Hansen TB, Deutch SR, Svendsen SW. Proteomics perspectives in rotator cuff research: a systematic review of gene expression and protein composition in human tendinopathy. PLoS One 2015; 10 (04) e0119974
• 28 Chung SW, Choi BM, Kim JY. et al. Altered Gene and Protein Expressions in Torn Rotator Cuff Tendon Tissues in Diabetic Patients. Arthroscopy 2017; 33 (03) 518-526.e1
• 29 Leal MF, Caires Dos Santos L, Martins de Oliveira A. et al. Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears. PLoS One 2017; 12 (09) e0184141
• 30 Kluger R, Burgstaller J, Vogl C, Brem G, Skultety M, Mueller S. Candidate gene approach identifies six SNPs in tenascin-C (TNC) associated with degenerative rotator cuff tears. J Orthop Res 2017; 35 (04) 894-901
• 31 Ahn JO, Chung JY, Kim DH, Im W, Kim SH. Differences of RNA Expression in the Tendon According to Anatomic Outcomes in Rotator Cuff Repair. Am J Sports Med 2017; 45 (13) 2995-3003
• 32 Treviño EA, McFaline-Figueroa J, Guldberg RE, Platt MO, Temenoff JS. Full-thickness rotator cuff tear in rat results in distinct temporal expression of multiple proteases in tendon, muscle, and cartilage. J Orthop Res 2019; 37 (02) 490-502
• 33 Lee YS, Kim JY, Kim HN, Lee DW, Chung SW. Gene Expression Patterns Analysis in the Supraspinatus Muscle after a Rotator Cuff Tear in a Mouse Model. BioMed Res Int 2018; 2018: 5859013
• 34 Santoro Belangero P, Antônio Figueiredo E, Cohen C. et al. Changes in the expression of matrix extracellular genes and TGFB family members in rotator cuff tears. J Orthop Res 2018; 36 (09) 2542-2553
• 35 Ren YM, Duan YH, Sun YB, Yang T, Tian MQ. Bioinformatics analysis of differentially expressed genes in rotator cuff tear patients using microarray data. J Orthop Surg Res 2018; 13 (01) 284
• 36 Thankam FG, Boosani CS, Dilisio MF, Gross RM, Agrawal DK. Genes interconnecting AMPK and TREM-1 and associated microRNAs in rotator cuff tendon injury. Mol Cell Biochem 2019; 454 (1-2): 97-109
• 37 Foëx BA. Three generations of recurrent dislocated shoulders. Emerg Med J 2001; 18 (02) 148-149
• 38 Imazato Y. [Etiological considerations of the loose shoulder from a biochemical point of view--biochemical studies on collagen from deltoid and pectoral muscles and skin]. Nippon Seikeigeka Gakkai Zasshi 1992; 66 (10) 1006-1015
• 39 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 (12) 2432-2436
• 40 Collins M, Posthumus M, Schwellnus MP. The COL1A1 gene and acute soft tissue ruptures. Br J Sports Med 2010; 44 (14) 1063-1064
• 41 Belangero PS, Leal MF, de Castro Pochini A, Andreoli CV, Ejnisman B, Cohen M. Profile of collagen gene expression in the glenohumeral capsule of patients with traumatic anterior instability of the shoulder. Rev Bras Ortop 2014; 49 (06) 642-646
• 42 Belangero PS, Leal MF, Figueiredo EA. et al. Gene expression analysis in patients with traumatic anterior shoulder instability suggests deregulation of collagen genes. J Orthop Res 2014; 32 (10) 1311-1316
• 43 Belangero PS, Leal MF, Cohen C. et al. Expression analysis of genes involved in collagen cross-linking and its regulation in traumatic anterior shoulder instability. J Orthop Res 2016; 34 (03) 510-517
• 44 Belangero PS, Leal MF, Figueiredo EA. et al. Differential expression of extracellular matrix genes in glenohumeral capsule of shoulder instability patients. Connect Tissue Res 2016; 57 (04) 290-298
• 45 Cohen C, Ejnisman B. Epidemiology of frozen shoulder. In: Itoi E, Arce G, Bain GI, Diercks RL, Guttmann D, Imhoff AB. et al. Shoulder stiffness. Berlin: Springer Verlag; 2015: 21-30
• 46 Hand GC, Athanasou NA, Matthews T, Carr AJ. The pathology of frozen shoulder. J Bone Joint Surg Br 2007; 89 (07) 928-932
• 47 Hakim AJ, Cherkas LF, Spector TD, MacGregor AJ. Genetic associations between frozen shoulder and tennis elbow: a female twin study. Rheumatology (Oxford) 2003; 42 (06) 739-742
• 48 Hirschhorn P, Schmidt JM. Frozen shoulder in identical twins. Joint Bone Spine 2000; 67 (01) 75-76
• 49 Larsen S, Krogsgaard DG, Aagaard Larsen L, Iachina M, Skytthe A, Frederiksen H. Genetic and environmental influences in Dupuytren's disease: a study of 30,330 Danish twin pairs. J Hand Surg Eur Vol 2015; 40 (02) 171-176
• 50 Bunker TD, Anthony PP. The pathology of frozen shoulder. A Dupuytren-like disease. J Bone Joint Surg Br 1995; 77 (05) 677-683
• 51 Williams FM, Kalson NS, Fabiane SM, Mann DA, Deehan DJ. Joint Stiffness Is Heritable and Associated with Fibrotic Conditions and Joint Replacement. PLoS One 2015; 10 (07) e0133629
• 52 Lubis AM, Lubis VK. Matrix metalloproteinase, tissue inhibitor of metalloproteinase and transforming growth factor-beta 1 in frozen shoulder, and their changes as response to intensive stretching and supervised neglect exercise. J Orthop Sci 2013; 18 (04) 519-527
• 53 Bunker TD, Reilly J, Baird KS, Hamblen DL. Expression of growth factors, cytokines and matrix metalloproteinases in frozen shoulder. J Bone Joint Surg Br 2000; 82 (05) 768-773
• 54 Cohen C, Leal MF, Belangero PS. et al. The roles of Tenascin C and Fibronectin 1 in adhesive capsulitis: a pilot gene expression study. Clinics (São Paulo) 2016; 71 (06) 325-331
• 55 Brown ID, Kelly IG, McInnes IB. Detection of matrix metalloproteinases in primary frozen shoulders. J Bone Joint Surg Br 2008; 90 (Suppl. 02) 364
• 56 Kabbabe B, Ramkumar S, Richardson M. Cytogenetic analysis of the pathology of frozen shoulder. Int J Shoulder Surg 2010; 4 (03) 75-78
• 57 Xu Q, Gai PY, Lv HL, Li GR, Liu XY. Association of MMP3 genotype with susceptibility to frozen shoulder: a case-control study in a Chinese Han population. Genet Mol Res 2016; 15 (01)
• 58 Chen W, Meng J, Qian H. et al. A Study of IL-1β, MMP-3, TGF-β1, and GDF5 Polymorphisms and Their Association with Primary Frozen Shoulder in a Chinese Han Population. BioMed Res Int 2017; 2017: 3681645
• 59 Cohen C, Leal MF, Loyola LC. et al. Genetic variants involved in extracellular matrix homeostasis play a role in the susceptibility to frozen shoulder: A case-control study. J Orthop Res 2019; 37 (04) 948-956
• 60 Johnston P, Chojnowski AJ, Davidson RK, Riley GP, Donell ST, Clark IM. A complete expression profile of matrix-degrading metalloproteinases in Dupuytren's disease. J Hand Surg Am 2007; 32 (03) 343-351