Summary: | Structural variations such as copy number variants (CNVs) have been associated with multiple autoimmune diseases. In this study, we explored the association of the Fc gamma receptor 3B gene (<i>FCGR3B</i>) copy number variation (CNV) with rheumatoid arthritis (RA) susceptibility and related serological traits in the Pakistani population. We also performed a meta-analysis of four published <i>FCGR3B</i> CNV studies along with the current study. A total of 927 subjects (597 RA cases, 330 healthy controls) were recruited from three rheumatology centers in Pakistan. Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) were measured in RA patients. <i>FCGR3B</i> copy number was assayed using the TaqMan<sup>®</sup> CN assay (Hs04211858_cn, Applied Biosystems, Foster City, CA, USA) and the copy number was estimated by using CopyCaller<sup>®</sup> software (version 2.1; Applied Biosystems, USA). Logistic regression was applied to calculate the odds ratio (OR) of RA risk associated with <i>FCGR3B</i> CNV using sex and age as covariates in R. Meta-analysis on four previously published studies and the current study was performed using the random-effect model. We observed a significant association between <i>FCGR3B</i> copy number < 2 and RA susceptibility (OR = 1.53; 95% CI: 1.05 to 2.22; <i>p</i> = 0.0259) and anti-CCP seropositivity (OR 2.56; 95% CI: 1.34 to 4.89; <i>p</i> = 0.0045). A non-significant association of <i>FCGR3B</i> copy number < 2 was also observed between increased rheumatoid factor (RF) seropositivity (OR = 1.74; 95% CI:0.93 to 3.26; <i>p</i> = 0.0816). Meta-analysis on 13,915 subjects (7005 RA cases and 6907 controls) also showed significant association of copy number < 2 with the increased risk of RA (OR = 1.30; 95% CI: 1.07 to 1.56; <i>p</i> = 0.00671). <i>FCGR3B</i> copy number < 2 is associated with increased RA risk and anti-CCP seropositivity.
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