Abstract
Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis (odds ratio = 2.15, P = 0.00000085). This polymorphism alters the binding affinity of nuclear factor-kappaB and regulates FCRL3 expression. We observed high FCRL3 expression on B cells and augmented autoantibody production in individuals with the disease-susceptible genotype. We also found associations between the SNP and susceptibility to autoimmune thyroid disease and systemic lupus erythematosus. FCRL3 may therefore have a pivotal role in autoimmunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Arthritis, Rheumatoid / genetics*
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / metabolism
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Autoimmunity / genetics*
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Autoimmunity / immunology
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Autoimmunity / physiology
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Case-Control Studies
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Chromosomes, Human, Pair 1
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Gene Expression Regulation / physiology
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HLA-DR Antigens / genetics
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HLA-DR Antigens / immunology
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HLA-DRB1 Chains
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Humans
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Linkage Disequilibrium
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Molecular Sequence Data
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Multigene Family
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Mutation
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Polymorphism, Single Nucleotide
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Receptors, Immunologic / genetics*
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Receptors, Immunologic / metabolism
Substances
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FCRL3 protein, human
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HLA-DR Antigens
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HLA-DRB1 Chains
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Receptors, Immunologic