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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2019

Open Access 01-12-2019 | Painful Arc | Research article

Genetic basis of rotator cuff injury: a systematic review

Authors: Umile Giuseppe Longo, Vincenzo Candela, Alessandra Berton, Giuseppe Salvatore, Andrea Guarnieri, Joseph DeAngelis, Ara Nazarian, Vincenzo Denaro

Published in: BMC Medical Genetics | Issue 1/2019

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Abstract

Background

Rotator cuff disease is a widespread musculoskeletal pathology and a major cause of shoulder pain. Studies on familial predisposition suggest that genetic plays a role in the pathogenesis of rotator cuff disease. Several genes are responsible for rotator cuff disease. The aim of this study was to perform a systematic review on genetic association between rotator cuff disease and genes variations.

Methods

A systematic review of the literature was performed, in accordance with the PRISMA guidelines. PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases were searched comprehensively using the keywords: “Rotator cuff”, “Gene”, “Genetic”, “Predisposition”, “Single-nucleotide polymorphism” and “Genome-wide association”.

Results

8 studies investigating genes variations associated with rotator cuff tears were included in this review. 6 studies were case-control studies on candidate genes and 2 studies were GWASs. A significant association between SNPs and rotator cuff disease was found for DEFB1, FGFR1, FGFR3, ESRRB, FGF10, MMP-1, TNC, FCRL3, SASH1, SAP30BP, rs71404070 located next to cadherin8. Contradictory results were reported for MMP-3.

Conclusion

Further investigations are warranted to identify complete genetic profiles of rotator cuff disease and to clarify the complex interaction between genes, encoded proteins and environment. This may lead to individualized strategies for prevention and treatment of rotator cuff disease.

Level of evidence

Level IV, Systematic Review.
Literature
1.
Goodier HC, Carr AJ, Snelling SJ, Roche L, Wheway K, Watkins B, Dakin SG. Comparison of transforming growth factor beta expression in healthy and diseased human tendon. Arthritis Res Ther. 2016;18:48.CrossRef
2.
Longo UG, Salvatore G, Rizzello G, Berton A, Ciuffreda M, Candela V, Denaro V. The burden of rotator cuff surgery in Italy: a nationwide registry study. Arch Orthop Trauma Surg. 2017;137(2):217–24.CrossRef
3.
Longo UG, Berton A, Papapietro N, Maffulli N, Denaro V. Epidemiology, genetics and biological factors of rotator cuff tears. Med Sport Sci. 2012;57:1–9.PubMed
4.
Del Buono A, Oliva F, Longo UG, Rodeo SA, Orchard J, Denaro V, Maffulli N. Metalloproteases and rotator cuff disease. J Shoulder Elb Surg. 2012;21(2):200–8.CrossRef
5.
Longo UG, Petrillo S, Rizzello G, Candela V, Denaro V. Deltoid muscle tropism does not influence the outcome of arthroscopic rotator cuff repair. Musculoskelet Surg. 2016;100(3):193–8.CrossRef
6.
Longo UG, Forriol F, Campi S, Maffulli N, Denaro V. Animal models for translational research on shoulder pathologies: from bench to bedside. Sports Med Arthrosc Rev. 2011;19(3):184–93.CrossRef
7.
Longo UG, Franceschi F, Ruzzini L, Rabitti C, Morini S, Maffulli N, Forriol F, Denaro V. Light microscopic histology of supraspinatus tendon ruptures. Knee Surg Sports Traumatol Arthrosc. 2007;15(11):1390–4.CrossRef
8.
Linaker CH, Walker-Bone K. Shoulder disorders and occupation. Best Pract Res Clin Rheumatol. 2015;29(3):405–23.CrossRef
9.
Tashjian RZ, Hollins AM, Kim HM, Teefey SA, Middleton WD, Steger-May K, Galatz LM, Yamaguchi K. Factors affecting healing rates after arthroscopic double-row rotator cuff repair. Am J Sports Med. 2010;38(12):2435–42.CrossRef
10.
Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA. The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. J Bone Joint Surg Am. 2006;88(8):1699–704.CrossRef
11.
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(5):1136–42.CrossRef
12.
Harvie P, Ostlere SJ, Teh J, McNally EG, Clipsham K, Burston BJ, Pollard TC, Carr AJ. Genetic influences in the aetiology of tears of the rotator cuff. Sibling risk of a full-thickness tear. J Bone Joint Surg. 2004;86(5):696–700.CrossRef
13.
Roberti M, Mustich A, Gadaleta MN, Cantatore P. Identification of two homologous mitochondrial DNA sequences, which bind strongly and specifically to a mitochondrial protein of Paracentrotus lividus. Nucleic Acids Res. 1991;19(22):6249–54.CrossRef
14.
15.
Buskila D. Genetics of chronic pain states. Best Pract Res Clin Rheumatol. 2007;21(3):535–47.CrossRef
16.
Gwilym SE, Watkins B, Cooper CD, Harvie P, Auplish S, Pollard TC, Rees JL, Carr AJ. Genetic influences in the progression of tears of the rotator cuff. J Bone Joint Surg. 2009;91(7):915–7.CrossRef
17.
Longo UG, Ronga M, Maffulli N. Acute ruptures of the achilles tendon. Sports Med Arthrosc Rev. 2009;17(2):127–38.CrossRef
18.
Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gotzsche PC, Lang T, Consort G. The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med. 2001;134(8):663–94.CrossRef
19.
Teerlink CC, Cannon-Albright LA, Tashjian RZ. Significant association of full-thickness rotator cuff tears and estrogen-related receptor-beta (ESRRB). J Shoulder Elbow Surg/ American Shoulder and Elbow Surgeons [et al]. 2015;24(2):e31–5.CrossRef
20.
Motta Gda R, Amaral MV, Rezende E, Pitta R, Vieira TC, Duarte ME, Vieira AR, Casado PL. Evidence of genetic variations associated with rotator cuff disease. J Shoulder Elbow Surg. 2014;23(2):227–35.CrossRef
21.
Assuncao JH, Godoy-Santos AL, Dos Santos M, 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(7):1904–10.CrossRef
22.
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(4):894–901.CrossRef
23.
Longo UG, Margiotti K, Petrillo S, Rizzello G, Fusilli C, Maffulli N, De Luca A, Denaro V. Genetics of rotator cuff tears: no association of col5a1 gene in a case-control study. BMC Med Genet. 2018;19(1):217.CrossRef
24.
Salles JI, Lopes LR, Duarte MEL, Morrissey D, Martins MB, Machado DE, Guimaraes JAM, Perini JA. Fc receptor-like 3 (−169T>C) polymorphism increases the risk of tendinopathy in volleyball athletes: a case control study. BMC Med Genet. 2018;19(1):119.CrossRef
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/ American Shoulder and Elbow Surgeons [et al]. 2016;25(2):174–9.CrossRef
26.
Roos TR, Roos AK, Avins AL, Ahmed MA, Kleimeyer JP, Fredericson M, Ioannidis JPA, Dragoo JL, Kim SK. Genome-wide association study identifies a locus associated with rotator cuff injury. PLoS One. 2017;12(12):e0189317.CrossRef
27.
Longo UG, Berton A, Khan WS, Maffulli N, Denaro V. Histopathology of rotator cuff tears. Sports Med Arthrosc Rev. 2011;19(3):227–36.CrossRef
28.
Denaro V, Ruzzini L, Longo UG, Franceschi F, De Paola B, Cittadini A, Maffulli N, Sgambato A. Effect of dihydrotestosterone on cultured human tenocytes from intact supraspinatus tendon. Knee Surg Sports Traumatol Arthrosc. 2010;18(7):971–6.CrossRef
29.
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/ American Shoulder and Elbow Surgeons [et al]. 2017;26(6):1103–12.CrossRef
30.
Denaro V, Ruzzini L, Barnaba SA, Longo UG, Campi S, Maffulli N, Sgambato A. Effect of pulsed electromagnetic fields on human tenocyte cultures from supraspinatus and quadriceps tendons. Am J Phys Med Rehabil. 2011;90(2):119–27.CrossRef
31.
Ben Said M, Ayedi L, Mnejja M, Hakim B, Khalfallah A, Charfeddine I, Khifagi C, Turki K, Ayadi H, Benzina Z, et al. A novel missense mutation in the ESRRB gene causes DFNB35 hearing loss in a Tunisian family. Eur J Med Genet. 2011;54(6):e535–41.CrossRef
32.
van der Laan S, Tsanov N, Crozet C, Maiorano D. High Dub3 expression in mouse ESCs couples the G1/S checkpoint to pluripotency. Mol Cell. 2013;52(3):366–79.CrossRef
33.
Lundgreen K, Lian O, Scott A, Engebretsen L. Increased levels of apoptosis and p53 in partial-thickness supraspinatus tendon tears. Knee Surg Sports Traumatol Arthrosc. 2013;21(7):1636–41.CrossRef
34.
Millar NL, Reilly JH, Kerr SC, Campbell AL, Little KJ, Leach WJ, Rooney BP, Murrell GA, McInnes IB. Hypoxia: a critical regulator of early human tendinopathy. Ann Rheum Dis. 2012;71(2):302–10.CrossRef
35.
Mokone GG, Gajjar M, September AV, Schwellnus MP, Greenberg J, Noakes TD, Collins M. The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with achilles tendon injuries. Am J Sports Med. 2005;33(7):1016–21.CrossRef
36.
Saunders CJ, van der Merwe L, Posthumus M, Cook J, Handley CJ, Collins M, September AV. Investigation of variants within the COL27A1 and TNC genes and Achilles tendinopathy in two populations. J Orthop Res. 2013;31(4):632–7.CrossRef
37.
September AV, Cook J, Handley CJ, van der Merwe L, Schwellnus MP, Collins M. Variants within the COL5A1 gene are associated with Achilles tendinopathy in two populations. Br J Sports Med. 2009;43(5):357–65.CrossRef
38.
Altinisik J, Meric G, Erduran M, Ates O, Ulusal AE, Akseki D. The BstUI and DpnII variants of the COL5A1 gene are associated with tennis elbow. Am J Sports Med. 2015;43(7):1784–9.CrossRef
39.
Godoy-Santos A, Cunha MV, Ortiz RT, Fernandes TD, Mattar R Jr, dos Santos MC. MMP-1 promoter polymorphism is associated with primary tendinopathy of the posterior tibial tendon. J Orthop Res. 2013;31(7):1103–7.CrossRef
40.
Swainson LA, Mold JE, Bajpai UD, McCune JM. Expression of the autoimmune susceptibility gene FcRL3 on human regulatory T cells is associated with dysfunction and high levels of programmed cell death-1. J Immunol. 2010;184(7):3639–47.CrossRef
41.
Chistiakov DA, Chistiakov AP. Is FCRL3 a new general autoimmunity gene? Hum Immunol. 2007;68(5):375–83.CrossRef
42.
Nagata S, Ise T, Pastan I. Fc receptor-like 3 protein expressed on IL-2 nonresponsive subset of human regulatory T cells. J Immunol. 2009;182(12):7518–26.CrossRef
43.
Meng Q, Zheng M, Liu H, Song C, Zhang W, Yan J, Qin L, Liu X. SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell. Mol Cell Biochem. 2013;373(1–2):201–10.CrossRef
Metadata
Title
Genetic basis of rotator cuff injury: a systematic review
Authors
Umile Giuseppe Longo
Vincenzo Candela
Alessandra Berton
Giuseppe Salvatore
Andrea Guarnieri
Joseph DeAngelis
Ara Nazarian
Vincenzo Denaro
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-019-0883-y

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