title: Significant association of full-thickness rotator cuff tears and estrogen-related receptor-β (ESRRB).
abstract: BACKGROUND
  The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Variants of estrogen-related receptor-β (ESRRB) have been previously associated with rotator cuff disease. The purpose of the present study was to confirm the association between multiple candidate genes, including ESRRB, and rotator cuff disease in an independent set of patients with rotator cuff tear.
  
  
  METHODS
  The Illumina 5M (Illumina Inc, San Diego, CA, USA) single nucleotide polymorphism (SNP) platform was used to genotype 175 patients with rotator cuff tear. Genotypes were used to select a set of 2595 genetically matched Caucasian controls available from the Illumina iControls database. Tests of association were performed with Genome-wide Efficient Mixed Model Association (GEMMA) software at 69 SNPs that fell within 20 kb of 6 candidate genes (DEFB1, DENND2C, ESRRB, FGF3, FGF10, and FGFR1).
  
  
  RESULTS
  Tests of association revealed 1 significantly associated SNP occurring in ESRRB (rs17583842; P = 4.4E-4). Another SNP within ESRRB (rs7157192) had a nominal P value of 7.8E-3. FastPHASE software estimated 2 frequent haplotypes among 54 individuals who carried both risk alleles at these 2 SNPs. The first haplotype had a frequency of 13.9% (n = 15) in risk-allele carriers and only 2.2% in controls (odds ratio, 6.9; 95% confidence interval, 3.9-2.2). The second haplotype had a frequency of 12.9% in risk-allele carriers and only 2.7% in controls (odds ratio, 5.3; 95% confidence interval, 3.0-9.5).
  
  
  CONCLUSIONS
  The significant association and the presence of high-risk haplotypes identified in the ESRRB gene confirm the association of variants in ESRRB and rotator cuff disease.
authors.affiliation: Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. Electronic address: craig.teerlink@utah.edu.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Teerlink
authors.affiliation: Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.affiliation: George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA; Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Tashjian
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics*; D000070636:Rotator Cuff Injuries; D012421:Rupture / Q000235:genetics
chemical_list: C490918:ESRRB protein, human; D011960:Receptors, Estrogen
keywords: ESRRB; Rotator cuff disease; confirmation study; genetic association