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

Yuta Kochi, Ryo Yamada, Akari Suzuki, John B. Harley, Senji Shirasawa, Tetsuji Sawada, Sang Cheol Bae, Shinya Tokuhiro, Xiaotian Chang, Akihiro Sekine, Atsushi Takahashi, Tatsuhiko Tsunoda, Yozo Ohnishi, Kenneth M. Kaufman, Changsoo Paul Kang, Changwon Kang, Shigeru Otsubo, Wako Yumura, Akio Mimori, Takao KoikeYusuke Nakamura, Takehiko Sasazuki, Kazuhiko Yamamoto

Research output: Contribution to journalArticle

296 Citations (Scopus)

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-ê 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.

Original languageEnglish
Pages (from-to)478-485
Number of pages8
JournalNature genetics
Volume37
Issue number5
DOIs
Publication statusPublished - May 2005

All Science Journal Classification (ASJC) codes

  • Genetics

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    Kochi, Y., Yamada, R., Suzuki, A., Harley, J. B., Shirasawa, S., Sawada, T., Bae, S. C., Tokuhiro, S., Chang, X., Sekine, A., Takahashi, A., Tsunoda, T., Ohnishi, Y., Kaufman, K. M., Kang, C. P., Kang, C., Otsubo, S., Yumura, W., Mimori, A., ... Yamamoto, K. (2005). A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nature genetics, 37(5), 478-485. https://doi.org/10.1038/ng1540