Abstract
IntroductionLow 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.MethodThe 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.ResultsA 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).ConclusionsThe 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.
Highlights
Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease
A significant association between rheumatoid arthritis (RA) and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared with 6.2% in controls
A meta-analysis including six previous studies confirmed an association between RA and low FCGR3B CN
Summary
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. Fc gamma receptors are present predominantly on myeloid cells and interact with the Fc portion of the IgG molecule They can be either stimulatory or inhibitory and play an integral role in the identification and destruction of both endogenous and foreign opsonised material. The aim of our study was to determine whether there is an association between CN of the FCGR3B gene and RA, compared with population controls The identification of such a relationship and confirmation of a low CN of FCGR3B as a susceptibility factor would contribute to our evolving understanding of the pathogenesis of RA
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