Low copy numbers of FCGR3A and FCGR3B associated with Chinese patients with SLE and AASV

Low-affinity Fc receptors (FcR) act as key mediators of the pathogenic effects of autoantibodies. In this study, we aimed to determine whether copy number variations (CNVs) in FCGR3A and FCGR3B were associated with systemic lupus nephritis (SLE) and ANCA-associated systemic vasculitis (AASV) in Chinese individuals. A total of 1118 individuals were enrolled, including 415 SLE patients, 139 AASV patients, and 564 healthy controls. FCGR3A and FCGR3B copy numbers (CNs) were determined by both a paralogue ratio test and TaqMan quantitative PCR assay. In the susceptibility associations, a low FCGR3B CN was significantly associated with SLE (p=5.01x10(-3); odds ratio (OR) 1.71; 95% confidence interval (CI) 1.17-2.48) and AASV (p=0.04; OR=1.72; 95% CI 1.02-2.88). A low FCGR3A CN was also significantly associated with SLE (p=6.02x10(-3); OR 2.72; 95% CI 1.30-5.71) and AASV (p=0.042; OR 2.64; 95% CI 1.00-6.93). Further subphenotype analysis revealed that low CNs of FCGR3A and FCGR3B were significantly associated with clinical manifestations in SLE and AASV patients. Therefore, in this case-control study, we identified low CNs of FCGR2A and FCGR3B to be common risk factors for SLE and AASV.Beijing Natural Science Foundation [7152148, 7131016]; National Science Foundation of China [81570629, 81270795, 81470945]; National Key Research and Development Program of China [2016YFC0904100]; National Key Technology RD Program [2013BAI09B14]; Natural Science Foundation for Innovation Research Group of China [81321064]; Natural Science Foundation for Excellent Young Scientists [813220065]; Capital of Clinical Characteristics and the Applied Research Fund [Z141107002514037]; Beijing Municipal Science and Technology for the Outstanding PhD Program [20121000110]; Chinese Society of Nephrology [15020030591]SCI(E)ARTICLE131383-13892