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

Manuela Fanciulli , Penny J Norsworthy , Enrico Petretto , Rong Dong , Lorraine Harper , Lavanya Kamesh , Joanne M Heward , Stephen C L Gough , Adam de Smith , Alexandra I F Blakemore , Philippe Froguel (1, 2, 3) , Catherine J Owen , Simon H S Pearce , Luis Teixeira , Loic Guillevin , Deborah S Cunninghame Graham (4, 5) , Charles D Pusey , H Terence Cook , Timothy J Vyse , Timothy J Aitman

1 GMM - Génétique des maladies multifactorielles
2 Section of Genomic Medicine
3 Genome Centre
4 OSU - Oregon State University
5 Dpt Civil, Environmental & Architectural Engineering, University of Kansas

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.

Domaines: Génétique humaine

Manuela Fanciulli, Penny J Norsworthy, Enrico Petretto, Rong Dong, Lorraine Harper, et al.. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity.. Nature Genetics, 2007, 39 (6), pp.721-3. ⟨10.1038/ng2046⟩. ⟨hal-00173649⟩