Clinical Orthopaedics and Related Research®

, Volume 475, Issue 7, pp 1904–1910 | Cite as

Matrix Metalloproteases 1 and 3 Promoter Gene Polymorphism Is Associated With Rotator Cuff Tear

  • Jorge H. Assunção
  • Alexandre L. Godoy-Santos
  • Maria Cristina L. G. dos Santos
  • Eduardo A. Malavolta
  • Mauro E. C. Gracitelli
  • Arnaldo A. Ferreira Neto
Clinical Research



Studies suggest that the collagen degeneration and disordered arrangement of collagen fibers in rotator cuff tears are associated with an increase in activity of matrix metalloproteases 1 and 3 (MMP-1 and MMP-3), and that MMP activity may be in part genetically mediated. The degree to which this might be clinically relevant in patients with rotator cuff tears has not been well characterized.


(1) Is genetic polymorphism of MMP-1 and MMP-3 associated with rotator cuff tears? (2) Are there haplotypes of MMP-1 and MMP-3 correlated with rotator cuff tears? (3) Compared with control subjects, do patients with rotator cuff tears have a higher proportion of relatives with the same disease?


We evaluated 64 patients with full-thickness rotator cuff tears and 64 asymptomatic control subjects. Patients younger 65 years, with nontraumatic tears, were included. The tear or integrity of the rotator cuff tear was evaluated by MRI or ultrasonography in all individuals. The patients and control subjects were paired by age. MMP-1 and MMP-3 genotypes were determined using the PCR-restriction fragment length polymorphism assays.


Genetic polymorphisms in MMP-1 and MMP-3 are associated with rotator cuff tear, in which individuals with rotator cuff tears have associated genotypes 1G/2G (patients, 32 of 64 [50%], control subjects, 16 of 64 [25%]; odds ratio [OR], 4.8; 95% CI, 2.1–11.0; p < 0.001) and 2G/2G were at great risk (patients, 15 of 64 [23%], control subjects, seven of 64 [11%]; OR, 5.2; 95% CI,1.8–14.9; p < 0.001), and patients with rotator cuff tears were associated with a higher proportion of 2G allele distribution (62 of 128 [48%] versus 30 of 128 [23%]; p < 0.001). Patients with the 5A/5A genotype are at greater risk of rotator cuff tear (patients, 15 of 64 [23%]; control subjects, four of 64 [6%]; OR, 5.5; 95% CI, 1.4–20.9; p = 0.021), and there was higher 5A allele distribution in patients with rotator cuff tears (patients, 68 of 128 [53%]; control subjects, 52 of 128 [41%]; p = 0.045). Individuals with the haplotype 2G/5A were more likely to have rotator cuff tears develop (patients, 42 of 64 [66%]; control subjects, 17 of 64 [27%]; OR, 5.3; 95% CI, 2.5-11.3; p < 0.001). Patients with rotator cuff tears reported, in higher number, the existence of relatives who previously had treatment for rotator cuff tears (19 of 64 [30%] versus four of 64 [6%]; OR, 6.3; 95% CI, 2.0-19.9; p = 0.001).


The genetic polymorphism of MMP-1 and MMP-3 is associated with rotator cuff tear. Individuals with haplotype 2G/5A were more susceptible to rotator cuff tears in the population studied.

Clinical Relevance

Knowledge of the genetic markers related to rotator cuff tears can enable identification of susceptible individuals and increase understanding of the pathogenesis of tendon degeneration.



Alberto Peters Bambirra MD, Ceci Obara Kurimori MD, and Marcelo Bordalo-Rodrigues PhD (all from the Department of Radiology, School of Medicine, University of São Paulo, São Paulo, Brazil), performed the MRI or ultrasonography examinations.


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Copyright information

© The Association of Bone and Joint Surgeons® 2017

Authors and Affiliations

  • Jorge H. Assunção
    • 1
  • Alexandre L. Godoy-Santos
    • 1
  • Maria Cristina L. G. dos Santos
    • 2
  • Eduardo A. Malavolta
    • 1
  • Mauro E. C. Gracitelli
    • 1
  • Arnaldo A. Ferreira Neto
    • 1
  1. 1.Department of Orthopedics and Traumatology, School of MedicineUniversity of São PauloSão PauloBrazil
  2. 2.Department of Cell BiologyUniversity Federal of ParanáCuritibaBrazil

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