FCGR3B copy number variation is associated with systemic lupus erythematosus risk in Afro-Caribbeans.

Abstract

To evaluate FCGR3B copy number variation (CNV) in African and European populations and to determine if FCGR3B copy number is associated with SLE and SLE nephritis risk in Afro-Caribbeans, adjusting for African genetic ancestry. We estimated FCGR3B to determine if there were ethnic variations in CNV (unrelated unadmixed Europeans and Africans). We then examined CNV at FCGR3B in relation to SLE and SLE nephritis within a case-control collection of 134 cases of SLE (37 with SLE nephritis) and 589 population controls of mainly Afro-Caribbean descent resident in Trinidad. We found a significant difference in copy number FCGR3B distribution between unadmixed African and European UK cohorts, with 27 (29%) vs 3 (5%) for those with low (0 or 1) copy FCGR3B, respectively, P = 0.002. In a Trinidadian SLE case-control study, low FCGR3B CNV was associated with SLE risk 1.7 (95% CI 1.1, 2.8), P = 0.02, which remained after adjustment for African genetic ancestry; odds ratios (ORs) 1.7 (95% CI 1.0, 2.8), P = 0.04. Our studies suggest that FCGR3B low copy number is associated with SLE risk in Afro-Caribbean populations independently of CNV due to African ancestry.