Gene variation linked to SLE and ANCA-associated vasculitis

Structural variation in the FCGR3B gene confers a very high risk of autoimmunity, "particularly for SLE", according to an advance online report.Structural variation is recognised as a rich source of genetic diversity in the human genome writes lead author Timothy Aitman (Imperial College, London), adding that during the past few years thousands of common copy number variants (CNVs) have been described.In their current study the investigators set out to determine whether the number of copies of the FCGR3B gene influences a person's chance of developing an autoimmune disease.Using two independent cohorts from the UK and France Aitman's team report a strong association between fewer than two copies of FCGR3B and the risk of developing systemic lupus erythematosus, microscopic polyangiitis and Wegener's granulomatosis."Our data show an association between low FCGR3B copy number and risk of development of SLE and ANCA-associated vasculitis, both of which have systemic inflammation as a key feature and commonly involve the glomerulus. In contrast, we did not find any significant association with Graves' or Addison's diseases, both of which are organ-specific autoimmune disorders, suggesting a different role for FCGR3B CNV in development of systemic and organ-specific autoimmunity."Overall, 2% of patients with autoimmunity had no copies of FCGR3B, compared with only 0.1% of controls, suggesting that "complete FCGR3B deficiency confers a very high risk of autoimmunity, particularly for SLE."In a related press release Aitman highlights how important gene copy number variation is in the "genetic predisposition to common human diseases". The group conclude, "the next step is to find out whether genes that are closely related to this susceptibility gene, FCGR3B, also vary in copy number and predispose to similar diseases."Reference...