Evidence of genetic variations associated with rotator cuff disease

J Shoulder Elbow Surg. 2014 Feb;23(2):227-35. doi: 10.1016/j.jse.2013.07.053. Epub 2013 Oct 12.


Background: Rotator cuff disease (RCD) is a complex process influenced by a multitude of factors, and a number of gene pathways are altered in rotator cuff tears. Polymorphisms in these genes can lead to an extended tendon degeneration process, which explains why subsets of patients are more susceptible to RCD.

Materials and methods: Twenty-three single-nucleotide polymorphisms within 6 genes involved in repair and degenerative processes (DEFB1, DENND2C, ESRRB, FGF3, FGF10, and FGFR1) were investigated in 410 patients, 203 with a diagnosis of RCD and 207 presenting with absence of RCD. Exclusion criteria were patients older than 60 years and younger than 45 years with a history of trauma, rheumatoid arthritis, autoimmune syndrome, pregnancy, and use of corticosteroids. Genomic DNA was obtained from saliva samples. Genetic markers were genotyped with TaqMan real-time polymerase chain reaction. The χ(2) test compared genotypes and haplotype differences between groups. Multivariate logistic regression analyzed the significance of many covariates and the incidence of RCD.

Results: Statistical analysis revealed female sex (P = .001; odds ratio, 2.07 [1.30-3.30]) and being white (P = .002; odds ratio, 1.88 [1.21-2.90]) to be risk factors for RCD development. A significant association of haplotypes CCTTCCAG in ESRRB (P = .05), CGACG in FGF3 (P = .01), CC in DEFB1 (P = .03), and FGFR1 rs13317 (P = .02) with RCD could be observed. Also, association between FGF10 rs11750845 (P = .03) and rs1011814 (P = .01) was observed after adjustment by ethnic group and sex.

Conclusions: Our work clearly supports the role of DEFB1, ESRRB, FGF3, FGF10, and FGFR1 genes in RCD. Identification of these variants can clarify causal pathways and provide a clue for therapeutic targets.

Keywords: Cross Sectional Study; Epidemiology Study; Level III; Rotator cuff disease; degenerative process; genetic; haplotype; polymorphism; tendon.

MeSH terms

  • Female
  • Genetic Variation
  • Humans
  • Male
  • Middle Aged
  • Muscular Diseases / diagnosis
  • Muscular Diseases / genetics*
  • Polymorphism, Single Nucleotide
  • Rotator Cuff Injuries
  • Rotator Cuff*
  • Tendinopathy / diagnosis
  • Tendinopathy / genetics*