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

Genes & Immunity volume 13, pages 458–460 (2012)Cite this article

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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.

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Acknowledgements

The Health Research Council of NZ and NZ Lottery Health are thanked for financial support. JM was funded by grant SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, by Redes Temáticas de Investigación Cooperativa Sanitaria Programme, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain, and by Fondo Europeo de Desarrollo Regional (FEDER).

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Author notes

  1. J Martin, T R D J Radstake and T R Merriman: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, University of Otago, Dunedin, New Zealand

    C McKinney & T R Merriman

  2. Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    J C A Broen, M C Vonk & T R D J Radstake

  3. Referral Center for Systemic Autoimmune Diseases, University of Milan, Milan, Italy

    L Beretta & R Scorza

  4. Department of Rheumatology, Lund University, Lund, Sweden

    R Hesselstrand

  5. Department of Dermatology, University of Cologne, Cologne, Germany

    N Hunzelmann

  6. Department of Rheumatology and Clinical Immunology, Charité University Hospital and German Rheumatism Research Centre, Leibniz, Germany

    G Riemekasten

  7. Internal Medicine Department, Hospital Valld′Hebron, Barcelona, Spain

    C P Simeon & V Fonollosa

  8. Rheumatology Division, Hospital 12 de Octubre, Madrid, Spain

    P E Carreira

  9. Internal Medicine Department, Hospital Universitario San Cecilio, Granada, Spain

    N Ortego-Centeno

  10. Rheumatology Division, Hospital Universitario Marques de Valdecilla, IFIMAV, Santander, Spain

    M A Gonzalez-Gay

  11. Servizio di Reumatologia ed Immunologia Clinica, Spedali Civili, Brescia, Italia

    P Airo

  12. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    M Coenen

  13. Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain

    J Martin

  14. Department of Rheumatology and Clinical Immunology, Utrecht Medical Center, Utrecht, The Netherlands

    T R D J Radstake

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  1. C McKinney
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  2. J C A Broen
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  3. M C Vonk
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  4. L Beretta
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  5. R Hesselstrand
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  7. G Riemekasten
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  8. R Scorza
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  9. C P Simeon
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  10. V Fonollosa
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  11. P E Carreira
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  12. N Ortego-Centeno
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  13. M A Gonzalez-Gay
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  14. P Airo
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  15. M Coenen
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  16. J Martin
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  17. T R D J Radstake
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  18. T R Merriman
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Corresponding author

Correspondence to T R Merriman.

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McKinney, C., Broen, J., Vonk, M. et al. Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis. Genes Immun 13, 458–460 (2012). https://doi.org/10.1038/gene.2012.15

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