title: Association of variation in Fcgamma receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples.
abstract: OBJECTIVE
  There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fcgamma receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of polymorphonuclear neutrophils (PMNs). Given recent evidence that low FCGR3B CN is a risk factor for systemic but not organ-specific autoimmune disease and the potential importance of PMN in the pathophysiology of rheumatoid arthritis (RA), the authors hypothesised that FCGR3B gene dosage influences susceptibility to RA.
  
  
  METHODS
  FCGR3B CN was measured in 643 cases of RA and 461 controls from New Zealand (NZ), with follow-up analysis in 768 cases and 702 controls from the Netherlands and 250 cases and 211 controls from the UK. All subjects were of Caucasian ancestry.
  
  
  RESULTS
  Significant evidence for an association between CN <2 and RA was observed in the Dutch cohort (OR 2.01 (95% CI 1.37 to 2.94), p=3 x 10-4) but not in the two smaller cohorts (OR 1.45 (95% CI 0.92 to 2.26), p=0.11 and OR 1.33 (95% CI 0.58 to 3.02), p=0.50 for the NZ and UK populations, respectively). The association was evident in a meta-analysis which included a previously published Caucasian sample set (OR 1.67 (95% CI 1.28 to 2.17), p=1.2 x 10-4).
  
  
  CONCLUSIONS
  One possible mechanism to explain the association between reduced FCGR3B CN and RA is the reduced clearance of immune complex during inflammation. However, it is not known whether the association between RA and FCGR3B CN is aetiological or acts as a proxy marker for another biologically relevant variant. More detailed examination of genetic variation within the FCGR gene cluster is required.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Cushla
authors.initials: C
authors.lastname: McKinney
authors.forename: Manuela
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Merriman
authors.forename: Amanda
authors.initials: A
authors.lastname: Phipps-Green
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gow
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Harrison
authors.forename: John
authors.initials: J
authors.lastname: Highton
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jones
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.forename: Sophia
authors.initials: S
authors.lastname: Steer
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Aitman
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D058851:GPI-Linked Proteins; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics*; D055815:Young Adult
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG
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