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Open Access Research article

Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta-analysis

Scott W Graf1*, Sue Lester1, Johannes C Nossent2, Catherine L Hill13, Susanna M Proudman4, Anita Lee4 and Maureen Rischmueller15

Author affiliations

1 Department of Rheumatology, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, South Australia 5011, Australia

2 Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø 9037, Tromsø, Norway

3 The Health Observatory, The University of Adelaide, Adelaide, South Australia 5005, Australia

4 Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia

5 Discipline of Medicine, The University of Adelaide, Adelaide, South Australia 5005 Australia

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Citation and License

Arthritis Research & Therapy 2012, 14:R28  doi:10.1186/ar3731

Published: 7 February 2012

Abstract

Introduction

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.

Method

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.