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

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.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).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.Variation in the copy number (CN) of genes within the human genome is an important source of genetic variation, and is defined as a sequence of DNA > 1 kb present in altered CN when compared with a reference genome [1]. In the diploid human genome, autosomal genes are normally present in two copies (one on each chromosome). When copy number variation (CNV) is present, however, the number of copies can vary from zero to greater than two. Studies have demonstrated a large number of genes within the human genome that display CNV in a relatively high frequency. CNV may be a major source of quantitative variation in expression, and has been proposed to contribute to phenotypic diversity and disease susceptibility [2-4]. There are increasing reports of associations between CNV of certain genes, cod