Download PDF
CC BY-NC-ND 4.0 · Rev Bras Ortop (Sao Paulo) 2020; 55(05): 537-542
DOI: 10.1055/s-0040-1702955
Artigo de Atualização
Ombro e Cotovelo

Aspectos genéticos nas afecções do ombro[∗]

Article in several languages: português | English
Carina Cohen 
1   Disciplina de Medicina do Esporte e Atividade Física , Centro de Traumatologia do Esporte, Universidade Federal de São Paulo, São Paulo, SP, Brasil
,
Eduardo A. Figueiredo 
1   Disciplina de Medicina do Esporte e Atividade Física , Centro de Traumatologia do Esporte, Universidade Federal de São Paulo, São Paulo, SP, Brasil
,
Paulo S. Belangero 
1   Disciplina de Medicina do Esporte e Atividade Física , Centro de Traumatologia do Esporte, Universidade Federal de São Paulo, São Paulo, SP, Brasil
,
Carlos Vicente Andreoli 
1   Disciplina de Medicina do Esporte e Atividade Física , Centro de Traumatologia do Esporte, Universidade Federal de São Paulo, São Paulo, SP, Brasil
,
Mariana Ferreira Leal 
2   Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, SP, Brasil
,
Benno Ejnisman 
1   Disciplina de Medicina do Esporte e Atividade Física , Centro de Traumatologia do Esporte, Universidade Federal de São Paulo, São Paulo, SP, Brasil
› Author Affiliations
› Further Information
   Permissions and Reprints

Resumo

A influência da herança genética tem sido cada vez mais investigada nas afecções do ombro, como a lesão do manguito rotador, instabilidade e ombro congelado. Ainda que os achados iniciais sejam pouco esclarecedores, é necessário construir progressivamente um banco de marcadores genéticos para catalogar perfis genômicos que, mais adiante, poderão contribuir para a previsão do risco da doença, desenvolvimento de melhores ferramentas de diagnóstico e tratamento. O presente artigo busca atualizar o que há de evidências de estudos genéticos na literatura para essas doenças, desde análises de polimorfismos, expressão de genes candidatos em tecidos e estudos de associação genômica ampla (GWAS, na sigla em inglês). Porém, é necessário apontar que existe grande dificuldade na replicação e utilização dos achados, principalmente em razão da falta de poder estatístico, da alta taxa de resultados falso-positivos e da grande quantidade de variáveis envolvidas.

Palavras-chave

ombro - polimorfismo genético - expressão gênica

∗ Trabalho desenvolvido na Disciplina de Medicina do Esporte e Atividade Física, Centro de Traumatologia do Esporte (CETE), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brasil.




Publication History

Received: 05 September 2019

Accepted: 12 November 2019

Article published online:
08 June 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Sociedade Brasileira de Ortopedia e Traumatologia. Published by Thieme Revinter Publicações Ltda
Rio de Janeiro, Brazil

 

  • Referências

  • 1 Lander ES, Linton LM, Birren B. et al. Initial sequencing and analysis of the human genome. Nature 2001; 409 (6822): 860-921
    CrossrefPubMedGoogle Scholar
  • 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. 2a. ed. Rio de Janeiro: Revinter; 2015: 5-56
    Google Scholar
  • 3 Frank CB. Ligament structure, physiology and function. J Musculoskelet Neuronal Interact 2004; 4 (02) 199-201
    Google Scholar
  • 4 Mitchell AL, Schwarze U, Jennings JF, Byers PH. Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS). Hum Mutat 2009; 30 (06) 995-1002
    CrossrefPubMedGoogle Scholar
  • 5 Chiquet-Ehrismann R, Tucker RP. Tenascins and the importance of adhesion modulation. Cold Spring Harb Perspect Biol 2011; 3 (05) a004960
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 37 Foëx BA. Three generations of recurrent dislocated shoulders. Emerg Med J 2001; 18 (02) 148-149
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 40 Collins M, Posthumus M, Schwellnus MP. The COL1A1 gene and acute soft tissue ruptures. Br J Sports Med 2010; 44 (14) 1063-1064
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefGoogle Scholar
  • 46 Hand GC, Athanasou NA, Matthews T, Carr AJ. The pathology of frozen shoulder. J Bone Joint Surg Br 2007; 89 (07) 928-932
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 48 Hirschhorn P, Schmidt JM. Frozen shoulder in identical twins. Joint Bone Spine 2000; 67 (01) 75-76
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 50 Bunker TD, Anthony PP. The pathology of frozen shoulder. A Dupuytren-like disease. J Bone Joint Surg Br 1995; 77 (05) 677-683
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 56 Kabbabe B, Ramkumar S, Richardson M. Cytogenetic analysis of the pathology of frozen shoulder. Int J Shoulder Surg 2010; 4 (03) 75-78
    CrossrefPubMedGoogle Scholar
  • 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) DOI: 10.4238/gmr.15017228.
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar