Association of variation in Fcgamma receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples.
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.
McKinney
Cushla
C
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Fanciulli
Manuela
M
Merriman
Marilyn E
ME
Phipps-Green
Amanda
A
Alizadeh
Behrooz Z
BZ
Koeleman
Bobby P C
BP
Dalbeth
Nicola
N
Gow
Peter J
PJ
Harrison
Andrew A
AA
Highton
John
J
Jones
Peter B
PB
Stamp
Lisa K
LK
Steer
Sophia
S
Barrera
Pilar
P
Coenen
Marieke J H
MJ
Franke
Barbara
B
van Riel
Piet L C M
PL
Vyse
Tim J
TJ
Aitman
Tim J
TJ
Radstake
Timothy R D J
TR
Merriman
Tony R
TR
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
C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG
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