title: Association of a BMP5 microsatellite with knee osteoarthritis: case-control study.
abstract: BACKGROUND
  We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection.
  
  
  METHODS
  OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or symptoms of OA were genotyped for the D6S1276 microsatellite in intron 1 of BMP5. Genotype and mutiallelic trend tests were used to compare cases and controls.
  
  
  RESULTS
  Significant association was found between the microsatellite and knee OA in women (P from 3.1 x10-4 to 4.1 x10-4 depending on the test), but not in men. Three of the alleles showed significant differences between patients and controls, one of them of increased risk and two of protection. The gender association and the allele direction of change were very concordant with those previously reported for hip OA.
  
  
  CONCLUSIONS
  We have found association of knee OA in women with the D6S1276 functional microsatellite that modifies in cis the expression of BMP5 making this a sounder OA genetic factor and extending its involvement to other joints. This result also shows the interest of analysing other multiallelic polymorphisms.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodriguez-Fontenla
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
mesh_terms: D019645:Arthroplasty, Replacement, Knee; D055417:Bone Morphogenetic Protein 5 / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006115:Greece; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008390:Markov Chains; D018895:Microsatellite Repeats / Q000235:genetics*; D009010:Monte Carlo Method; D020370:Osteoarthritis, Knee / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D012737:Sex Factors; D013030:Spain; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: C525814:BMP5 protein, human; D055417:Bone Morphogenetic Protein 5