FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

被引：389

作者：

Fanciulli, Manuela

Norsworthy, Penny J.

Petretto, Enrico

Dong, Rong

Harper, Lorraine

Kamesh, Lavanya

Heward, Joanne M.

Gough, Stephen C. L.

de Smith, Adam

Blakemore, Alexandra I. F.

Owen, Catherine J.

Pearce, Simon H. S.

Teixeira, Luis

Guillevin, Loic

Graham, Deborah S. Cunninghame

Pusey, Charles D.

Cook, H. Terence

Vyse, Timothy J.

Aitman, Timothy J. ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Physiol Genom & Med Grp, UK Med Res Council, Clin Sci Ctr, London W12 0NN, England

[2] Univ Birmingham, Sch Med, Div Med Sci, Birmingham B15 277, W Midlands, England

[3] Univ Birmingham, Sch Med, Div Immun & Infect, Birmingham B15 277, W Midlands, England

[4] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sect Genom Med, Div Med, London W12 0NN, England

[5] Inst Pasteur, Inst Biol, CNRS, UMR 8090, F-59800 Lille, France

[6] Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 EBZ, Tyne & Wear, England

[7] Paris Descartes Univ, AP HP, Cochin Hosp, Dept Internal Med,Reference Ctr Vascul & System S, F-75679 Paris 14, France

[8] Univ London Imperial Coll Sci Technol & Med, Sect Mol Genet & Rheumatol, London W12 0NN, England

[9] Univ London Imperial Coll Sci Technol & Med, Sect Renal Med, London W12 0NN, England

[10] Univ London Imperial Coll Sci Technol & Med, Dept Histopathol, London W12 0NN, England

来源：

NATURE GENETICS | 2007年 / 39卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng2046

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK ( P = 3 x 10(-3)) and France ( P = 1.1 x 10(-4)). We did not observe this association in the organ- specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.

引用

页码：721 / 723

页数：3

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