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Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases

Genes & Immunity volume 11, pages 155–160 (2010)Cite this article

Abstract

Copy number variation (CNV) in the human genome is an important determinant of susceptibility to autoimmune diseases. Many autoimmune diseases share similar clinical and pathogenic features. Thus, CNVs of genes involved in immunity may serve as shared determinants of multiple autoimmune diseases. Here, we determined the association between CNV in the gene encoding FCGR3B with the risk of developing autoimmune diseases and whether the observed associations are modified by the CNV in CCL3L1 (CC chemokine ligand 3-like 1), a gene encoding a potent chemokine. In a cross-sectional study of 774 subjects, we estimated FCGR3B and CCL3L1 gene copy number in 146, 158 and 61 subjects with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS), respectively, and 409 healthy controls. The median gene dose of FCGR3B in the study population was two. FCGR3B copy number < or >2 was associated with an increased risk of SLE and primary SS but not RA. This association was mostly evident in subjects who also had two copies of CCL3L1. Thus, our data suggest that epistatic interactions between CNV of FCGR3B and CCL3L1, two immune response genes, may influence phenotypically related autoimmune diseases.

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Acknowledgements

We thank Robert A Clark and George Crawford for their institutional support; Jill King and Adriana Benavides for their help with the bioinformatics for designing the primers and probe. We thank the reviewers of this study for their critical review that greatly helped in improving our paper. This work was supported by the Voelcker Fund Scholar Award to Dr Sunil Ahuja from the Max and Minnie Tomerlin Voelcker Fund. SKA is also a recipient of the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research and the Doris Duke Distinguished Clinical Scientist Award. This work was also supported in part by the Rosario University, Bogota, Colombia.

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Authors and Affiliations

  1. South Texas Veterans Health Care System and Department of Medicine, The Veterans Administration Center for AIDS and HIV-1 infection, University of Texas Health Science Center, San Antonio, TX, USA

    M Mamtani, W He & S K Ahuja

  2. Center for Autoimmune Diseases Research (CREA), School of Medicine, Rosario University, Corporación para Investigaciones Biológicas, Medellin, Colombia

    J-M Anaya

  3. Departments of Microbiology, and Immunology, and Biochemistry,

    S K Ahuja

  4. , University of Texas Health Science Center, San Antonio, TX, USA

    S K Ahuja

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  1. M Mamtani
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Correspondence to S K Ahuja.

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Mamtani, M., Anaya, JM., He, W. et al. Association of copy number variation in the FCGR3B gene with risk of autoimmune diseases. Genes Immun 11, 155–160 (2010). https://doi.org/10.1038/gene.2009.71

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