Qi Y, Zhou X, Bu D, Hou P, Lv J, Zhang H
1 Renal Division, Peking University First Hospital, People's Republic of China.
2 Peking University Institute of Nephrology, People's Republic of China.
Lupus. 2017 Nov;26(13):1383-1389. doi: 10.1177/0961203317700485. Epub 2017 Mar 29.
Low-affinity Fcγ receptors (FcγR) 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 = 5.01 × 10; 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 = 6.02 × 10; 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.
低亲和力Fcγ受体（FcγR）是自身抗体致病作用的关键介质。在本研究中，我们旨在确定中国人群中FCGR3A和FCGR3B的拷贝数变异（CNV）是否与系统性红斑狼疮（SLE）和抗中性粒细胞胞浆抗体相关性系统性血管炎（AASV）有关。共纳入1118例个体，包括415例SLE患者、139例AASV患者和564例健康对照。通过旁系同源比率测试和TaqMan定量PCR测定法确定FCGR3A和FCGR3B的拷贝数（CN）。在易感性关联分析中，低FCGR3B拷贝数与SLE（p = 5.01×10；优势比（OR）1.71；95%置信区间（CI）1.17 - 2.48）和AASV（p = 0.04；OR = 1.72；95% CI 1.02 - 2.88）显著相关。低FCGR3A拷贝数也与SLE（p = 6.02×10；OR 2.72；95% CI 1.30 - 5.71）和AASV（p = 0.042；OR 2.64；95% CI 1.00 - 6.93）显著相关。进一步的亚表型分析显示，FCGR3A和FCGR3B的低拷贝数与SLE和AASV患者的临床表现显著相关。因此，在本病例对照研究中，我们确定FCGR2A和FCGR3B的低拷贝数是SLE和AASV的常见危险因素。
