title: Evidence of genetic variations associated with rotator cuff disease.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Orthopaedic Surgery, Center of Shoulder and Elbow Surgery, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
authors.forename: Geraldo da Rocha
authors.initials: Gda R
authors.lastname: Motta
authors.affiliation: Department of Orthopaedic Surgery, Center of Shoulder and Elbow Surgery, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil; Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
authors.forename: Marcus Vinícius
authors.initials: MV
authors.lastname: Amaral
authors.affiliation: Department of Orthopaedic Surgery, Center of Shoulder and Elbow Surgery, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rezende
authors.affiliation: Department of Orthopaedic Surgery, Center of Shoulder and Elbow Surgery, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Pitta
authors.affiliation: Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
authors.forename: Thays Cristine dos Santos
authors.initials: TC
authors.lastname: Vieira
authors.affiliation: Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil.
authors.forename: Maria Eugenia Leite
authors.initials: ME
authors.lastname: Duarte
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alexandre Rezende
authors.initials: AR
authors.lastname: Vieira
authors.affiliation: Research Division, National Institute of Traumatology and Orthopaedics, Rio de Janeiro, Brazil. Electronic address: pcasado@into.saude.gov.br.
authors.forename: Priscila Ladeira
authors.initials: PL
authors.lastname: Casado
mesh_terms: D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017006:Rotator Cuff; D000070636:Rotator Cuff Injuries; D052256:Tendinopathy / Q000175:diagnosis / Q000235:genetics*
keywords: Cross Sectional Study; Epidemiology Study; Level III; Rotator cuff disease; degenerative process; genetic; haplotype; polymorphism; tendon