Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta-analysis.
BACKGROUND
Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of the present study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA.


METHODS
The FCGR3B CN was determined using a custom Taqman® CN assay (Hs04211858; Applied Biosystems, Foster City, CA, USA) in 197 RA patients, recruited from a tertiary setting, and in 162 population matched controls. Odds ratios for low CN (< 2) and high CN (> 2), both relative to the normal diploid 2CN, were estimated by logistic regression.


RESULTS
A significant association between RA and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared with 6.2% in controls (odds ratio 2.5, 95% confidence interval 1.2 to 5.4, P = 0.017). No association was observed between low CN and the presence of rheumatoid factor, anti-cyclic citrullinated peptide antibodies or radiographic erosions in RA patients. A meta-analysis including six previous studies confirmed an association between RA and low FCGR3B CN (odds ratio 1.47, 95% confidence interval 1.13 to 1.92, P = 0.004).


CONCLUSIONS
The present study confirms that a low CN of the FCGR3B gene is associated with susceptibility to RA. The association may be stronger in patients recruited from a tertiary setting, which may relate to disease severity and/or complications. The mechanism of susceptibility remains unclear and further study is required.
Department of Rheumatology, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, South Australia 5011, Australia. graffa@hotmail.com
Scott W
SW
Graf
Sue
S
Lester
Johannes C
JC
Nossent
Catherine L
CL
Hill
Susanna M
SM
Proudman
Anita
A
Lee
Maureen
M
Rischmueller
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017452:Receptors, IgG / Q000235:genetics*; D062606:Tertiary Care Centers
C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D004247:DNA