title: Association of the Frizzled-related protein gene with symptomatic osteoarthritis at multiple sites.
abstract: OBJECTIVE
  To confirm the association of 2 variants of the Frizzled-related protein gene (FRZB) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes.
  
  
  METHODS
  An association analysis of 2 variants (R200W and R324G) of FRZB was performed in a random sample of 1,369 subjects (ages 55-70 years) from a population-based cohort (the Rotterdam Study) scored for radiographic characteristics of OA in the hip, hand, spine, and knee and in a patient population of Caucasian probands (ages 40-70 years) and their siblings selected for the presence of primary symptomatic OA at multiple sites.
  
  
  RESULTS
  The allele frequency of the 2 variants was not significantly different between subjects with hip radiographic OA (ROA) and controls. The frequency of the G allele of the R324G variant was significantly increased in subjects with generalized ROA from the Rotterdam Study (0.10) and in subjects from the Genetics, osteoARthritis and Progression study (0.11) compared with that in controls from the Rotterdam Study (0.08). Carriers of this G allele had increased susceptibility for generalized ROA (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 0.9-1.9, P = 0.10) or familial symptomatic OA at multiple sites (OR 1.6, 95% CI 1.1-2.3, P = 0.02).
  
  
  CONCLUSIONS
  Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes. A more extended OA phenotype may indeed be expected from genetic variation in an essential pathway of skeletal development such as Wnt signaling.
authors.affiliation: Leiden University Medical Center, Section of Molecular Epidemiology, Leiden, The Netherlands.
authors.forename: J L
authors.initials: JL
authors.lastname: Min
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: N
authors.initials: N
authors.lastname: Riyazi
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: J J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: A B
authors.initials: AB
authors.lastname: Seymour
authors.forename: H A
authors.initials: HA
authors.lastname: Pols
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D011446:Prospective Studies; D011859:Radiography; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins