Renal Division, Peking University First Hospital, Peking University Institute of Nephrology and Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, People's Republic of China.
Int Immunol. 2010 Jan;22(1):45-51. doi: 10.1093/intimm/dxp113. Epub 2009 Nov 27.
Anti-glomerular basement membrane antibody disease (anti-GBM disease) is a rare disorder characteristic of universally poor outcome. Fcgamma receptors (FcgammaRs) play important roles in anti-GBM disease based on evidence from animal models. Copy number variation (CNV) influences disease susceptibility. The FcgammaRs genes show CNV, and CNV of the FCGR3B gene is associated with glomerulonephritis in systemic lupus erythematosus and anti-neutrophil cytoplasmic antibody-associated small vasculitis. Here, we investigated CNV of three FCGR genes, including two (FCGR3A and FCGR3B) for activating FcgammaRs and one (FCGR2B) for inhibitory FcgammaR by duplex quantitative real-time PCR. Copy numbers were analyzed by Applied Biosystems CopyCaller Software v1.0. We first demonstrated the distribution of CNV of FCGR3A, FCGR3B and no CNV of FCGR2B in Chinese population (including 47 anti-GBM patients and 146 healthy controls). The frequency of CNV of FCGR3A was observed to be significantly higher than matched healthy controls (27.7 versus 12.3%, P = 0.013, odds ratio 1.21-6.10). Considering previous report about gene knock-out animal models and CNV effect of FCGR3A, we thus propose that CNV in members of FCGR family should have different roles in the pathogenesis of human anti-GBM disease.
抗肾小球基底膜抗体病（抗 GBM 病）是一种罕见的疾病，普遍预后不良。基于动物模型的证据，Fcγ 受体（FcγRs）在抗 GBM 病中发挥重要作用。拷贝数变异（CNV）影响疾病易感性。FcγRs 基因存在 CNV，FCGR3B 基因的 CNV与系统性红斑狼疮和抗中性粒细胞胞质抗体相关性小血管炎中的肾小球肾炎有关。在这里，我们通过双定量实时 PCR 研究了三个 FCGR 基因（包括两个激活 FcγRs 的 FCGR3A 和 FCGR3B 基因和一个抑制性 FcγR 的 FCGR2B 基因）的 CNV。通过 Applied Biosystems CopyCaller Software v1.0 分析拷贝数。我们首先在中国人群（包括 47 例抗 GBM 患者和 146 例健康对照者）中证实了 FCGR3A、FCGR3B 的 CNV 分布和 FCGR2B 无 CNV。观察到 FCGR3A 的 CNV 频率明显高于匹配的健康对照者（27.7%比 12.3%，P=0.013，比值比 1.21-6.10）。考虑到先前关于基因敲除动物模型和 FCGR3A 的 CNV 效应的报道，因此我们提出 FCGR 家族成员中的 CNV 在人类抗 GBM 病的发病机制中可能具有不同的作用。
