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

Nature Genetics volume 37, pages 478–485 (2005)Cite this article

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.

Author information

Authors and Affiliations

  1. Laboratory for Rheumatic Diseases, SNP Research Center, RIKEN, Yokohama, 230-0045, Japan

    Yuta Kochi, Ryo Yamada, Akari Suzuki, Shinya Tokuhiro, Xiaotian Chang & Kazuhiko Yamamoto

  2. Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, 113-0033, Japan

    Yuta Kochi, Tetsuji Sawada & Kazuhiko Yamamoto

  3. University of Oklahoma, Oklahoma City, 73104, Oklahoma, USA

    John B Harley & Kenneth M Kaufman

  4. US Department of Veterans Affairs, Oklahoma City, 73104, Oklahoma, USA

    John B Harley & Kenneth M Kaufman

  5. Oklahoma Medical Research Foundation, Oklahoma City, 73104, Oklahoma, USA

    John B Harley & Kenneth M Kaufman

  6. US Department of Veterans Affairs, Oklahoma City, 73104, Oklahoma, USA

    John B Harley & Kenneth M Kaufman

  7. International Medical Center of Japan, Tokyo, 162-8655, Japan

    Senji Shirasawa, Akio Mimori & Takehiko Sasazuki

  8. Department of Internal Medicine, Division of Rheumatology, the Hospital for Rheumatic Diseases, Hanyang University, Seoul, 133-792, Republic of Korea

    Sang-Cheol Bae

  9. Laboratory for Genotyping, SNP Research Center, RIKEN, Yokohama, 230-0045, Japan

    Akihiro Sekine

  10. Laboratory for Medical Informatics, SNP Research Center, RIKEN, Yokohama, 230-0045, Japan

    Atsushi Takahashi & Tatsuhiko Tsunoda

  11. Laboratory for SNP Analysis, SNP Research Center, RIKEN, Yokohama, 230-0045, Japan

    Yozo Ohnishi

  12. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea

    Changsoo Paul Kang & Changwon Kang

  13. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan

    Shigeru Otsubo & Yusuke Nakamura

  14. Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, 162-8666, Japan

    Wako Yumura

  15. Department of Medicine II, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan

    Takao Koike

  16. Research Group for Personalized Medicine, SNP Research Center, RIKEN, Yokohama, 230-0045, Japan

    Yusuke Nakamura

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  1. Yuta Kochi
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Correspondence to Ryo Yamada.

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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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