title: Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels.
abstract: OBJECTIVE
  Extensive joint hypermobility, lower serum cartilage oligomeric matrix protein (COMP) levels, and early-onset osteoarthritis (OA) are phenotypes of inherited pseudoachondroplasia and multiple epiphyseal dysplasia. However, few studies have evaluated the association between articular hypermobility and primary OA. We undertook the present study to evaluate this association and to test the hypothesis that COMP levels are associated with hypermobility in patients with OA and individuals without OA.
  
  
  METHODS
  Two separate cohorts were available for analysis, the CARRIAGE (CARolinas Region Interaction of Aging Genes and Environment) extended family and a subset of the GOGO (Genetics of Generalized Osteoarthritis) sibpair cohort. In the CARRIAGE family, we performed hand and knee examinations and hypermobility evaluations (Beighton criteria) and obtained sera for measurement of COMP and hyaluronan (HA). Data on COMP and HA levels and extensive joint radiographic and hypermobility data were also available for the GOGO cohort.
  
  
  RESULTS
  The prevalence of hypermobility was 13% in the CARRIAGE family and 5% in the GOGO cohort. In the CARRIAGE family, hypermobility was associated with a significantly reduced prevalence of hand (especially proximal interphalangeal joint) and knee OA and lower mean serum COMP levels, both in the total cohort and in non-hand-OA subgroups. These results were further validated in the GOGO subsets without radiographic OA, in which hypermobility was also associated with a significantly reduced mean serum COMP level (P < 0.0001 adjusted for age). Serum HA levels did not differ in relation to hypermobility in either cohort.
  
  
  CONCLUSIONS
  The present results indicate that there is an inverse relationship between hypermobility and hand and knee OA, and that hypermobility is associated with lower serum COMP levels. Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility.
authors.affiliation: Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chen
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Stabler
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Jordan
authors.forename: Virginia Byers
authors.initials: VB
authors.lastname: Kraus
mesh_terms: D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D064236:Cartilage Oligomeric Matrix Protein; D015331:Cohort Studies; D016326:Extracellular Matrix Proteins / Q000097:blood*; D006023:Glycoproteins / Q000097:blood*; D006225:Hand; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007593:Joint Instability / Q000453:epidemiology* / Q000378:metabolism*; D064235:Matrilin Proteins; D020370:Osteoarthritis, Knee / Q000453:epidemiology* / Q000378:metabolism*; D010641:Phenotype; D015995:Prevalence
chemical_list: D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D006820:Hyaluronic Acid