A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities

  • An Erratum to this article was published on 01 June 2005

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-κB 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.

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Figure 1: LD and association of the FCRL gene cluster.
Figure 2: Correlation of FCRL3 expression with allele and genotype.
Figure 3: Expression patterns of FCRL3 in human tissues and cells.

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Acknowledgements

We thank E. Kanno and other members of the Laboratory for Rheumatic Diseases for technical assistance; H. Kawakami for expertise in computer programming; M. Yukioka, S. Tohma, Y. Nishioka, T. Matsubara, S. Wakitani, R. Teshima, N. Ishikawa, K. Ito, K. Ito, K. Kuma, H. Tamai and T. Akamizu for clinical sample collection; M. Ishikawa and Y. Amasaki for preparation of the second population study; M. Nagashima and S. Yoshino for sampling rheumatoid arthritis synovium; and K. Nagatani and Y. Komagata for advice. This work was supported by grants from the Japanese Millennium Project, the US National Institutes of Health and the Korean Molecular and Cellular BioDiscovery Research Program.

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Correspondence to Ryo Yamada.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Stratification analysis of case-control samples using STRUCTURE software. (PDF 53 kb)

Supplementary Fig. 2

FCRL3 expression in RA synovium from two patients (RA2, RA3). (PDF 209 kb)

Supplementary Table 1

Case-control association analysis of the FCRL region. (PDF 21 kb)

Supplementary Table 2

Replication study of FCRL3 association with RA. (PDF 15 kb)

Supplementary Table 3

FCRL3 haplotype structure in different ethnic groups. (PDF 30 kb)

Supplementary Table 4

Primer sequences for ASTQ. (PDF 6 kb)

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Kochi, Y., Yamada, R., Suzuki, A. et al. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet 37, 478–485 (2005). https://doi.org/10.1038/ng1540

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