Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis

C. McKinney, J. C A Broen, M. C. Vonk, L. Beretta, R. Hesselstrand, N. Hunzelmann, G. Riemekasten, R. Scorza, C. P. Simeon, V. Fonollosa, P. E. Carreira, N. Ortego-Centeno, M. A. Gonzalez-Gay, P. Airo, M. Coenen, J. Martin, T. R D J Radstake, T. R. Merriman

Research output: Contribution to journalArticle

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 CN≥2. 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.

Original languageEnglish
Pages (from-to)458-460
Number of pages3
JournalGenes and Immunity
Volume13
Issue number6
DOIs
Publication statusPublished - Sep 2012

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Keywords

  • association
  • copy number
  • FCGR3B
  • polymorphism
  • systemic sclerosis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

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. (2012). Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis. Genes and Immunity, 13(6), 458-460. https://doi.org/10.1038/gene.2012.15