title: Copy number variation of FCGR3A rather than FCGR3B and FCGR2B is associated with susceptibility to anti-GBM disease.
abstract: 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.
authors: 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.
authors: Xu-jie
authors: XJ
authors: Zhou
authors: Ji-cheng
authors: JC
authors: Lv
authors: Ding-fang
authors: DF
authors: Bu
authors: Lei
authors: L
authors: Yu
authors: Yan-rong
authors: YR
authors: Yang
authors: Juan
authors: J
authors: Zhao
authors: Zhao
authors: Z
authors: Cui
authors: Rui
authors: R
authors: Yang
authors: Ming-Hui
authors: MH
authors: Zhao
authors: Hong
authors: H
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019867:Anti-Glomerular Basement Membrane Disease / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D002681:China; D056915:DNA Copy Number Variations; D005260:Female; D058851:GPI-Linked Proteins; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; C499173:FCGR2B protein, human; C496124:FCGR3A protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG