We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis.
- Authors
McKinney, C; Broen, J C A; Vonk, M C; Beretta, L; Hesselstrand, R; Hunzelmann, N; Riemekasten, G; Scorza, R; Simeon, C P; Fonollosa, V; Carreira, P E; Ortego-Centeno, N; Gonzalez-Gay, M A; Airo, P; Coenen, M; Martin, J; Radstake, T R D J; Merriman, T R
- Abstract
There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of 1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.
- Subjects
SYSTEMIC scleroderma; NEUTROPHILS; DISEASE susceptibility; DNA replication; INFLAMMATION; CLINICAL trials; DISEASE risk factors
- Publication
Genes & Immunity, 2012, Vol 13, Issue 6, p458
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/gene.2012.15