A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility

Yuta Kochi, Yukinori Okada, Akari Suzuki, Katsunori Ikari, Chikashi Terao, Atsushi Takahashi, Keiko Yamazaki, Naoya Hosono, Keiko Myouzen, Tatsuhiko Tsunoda, Naoyuki Kamatani, Tatsuya Furuichi, Shiro Ikegawa, Koichiro Ohmura, Tsuneyo Mimori, Fumihiko Matsuda, Takuji Iwamoto, Shigeki Momohara, Hisashi Yamanaka, Ryo YamadaMichiaki Kubo, Yusuke Nakamura, Kazuhiko Yamamoto

Research output: Contribution to journalArticle

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Abstract

Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here, through a genome-wide association study of rheumatoid arthritis, we identified a polymorphism in CCR6, the gene encoding chemokine (C-C motif) receptor 6 (a surface marker for Th17 cells) at 6q27, that was associated with rheumatoid arthritis susceptibility and was validated in two independent replication cohorts from Japan (rs3093024, a total of 7,069 individuals with rheumatoid arthritis (cases) and 20,727 controls, overall odds ratio = 1.19, P = 7.7 × 10-19). We identified a triallelic dinucleotide polymorphism of CCR6 (CCR6DNP) in strong linkage disequilibrium with rs3093024 that showed effects on gene transcription. The CCR6DNP genotype was correlated with the expression level of CCR6 and was associated with the presence of interleukin-17 (IL-17) in the sera of subjects with rheumatoid arthritis. Moreover, CCR6DNP was associated with susceptibility to Graves' and Crohn's diseases. These results suggest that CCR6 is critically involved in IL-17-driven autoimmunity in human diseases.

Original languageEnglish
Pages (from-to)515-519
Number of pages5
JournalNature Genetics
Volume42
Issue number6
DOIs
Publication statusPublished - 01-06-2010

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Rheumatoid Arthritis
Interleukin-17
CCR Receptors
Th17 Cells
Genome-Wide Association Study
Graves Disease
Linkage Disequilibrium
Autoimmunity
Crohn Disease
Genes
Autoimmune Diseases
Japan
Odds Ratio
Genotype
Serum

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Kochi, Y., Okada, Y., Suzuki, A., Ikari, K., Terao, C., Takahashi, A., ... Yamamoto, K. (2010). A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nature Genetics, 42(6), 515-519. https://doi.org/10.1038/ng.583
Kochi, Yuta ; Okada, Yukinori ; Suzuki, Akari ; Ikari, Katsunori ; Terao, Chikashi ; Takahashi, Atsushi ; Yamazaki, Keiko ; Hosono, Naoya ; Myouzen, Keiko ; Tsunoda, Tatsuhiko ; Kamatani, Naoyuki ; Furuichi, Tatsuya ; Ikegawa, Shiro ; Ohmura, Koichiro ; Mimori, Tsuneyo ; Matsuda, Fumihiko ; Iwamoto, Takuji ; Momohara, Shigeki ; Yamanaka, Hisashi ; Yamada, Ryo ; Kubo, Michiaki ; Nakamura, Yusuke ; Yamamoto, Kazuhiko. / A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. In: Nature Genetics. 2010 ; Vol. 42, No. 6. pp. 515-519.
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Kochi, Y, Okada, Y, Suzuki, A, Ikari, K, Terao, C, Takahashi, A, Yamazaki, K, Hosono, N, Myouzen, K, Tsunoda, T, Kamatani, N, Furuichi, T, Ikegawa, S, Ohmura, K, Mimori, T, Matsuda, F, Iwamoto, T, Momohara, S, Yamanaka, H, Yamada, R, Kubo, M, Nakamura, Y & Yamamoto, K 2010, 'A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility', Nature Genetics, vol. 42, no. 6, pp. 515-519. https://doi.org/10.1038/ng.583

A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. / Kochi, Yuta; Okada, Yukinori; Suzuki, Akari; Ikari, Katsunori; Terao, Chikashi; Takahashi, Atsushi; Yamazaki, Keiko; Hosono, Naoya; Myouzen, Keiko; Tsunoda, Tatsuhiko; Kamatani, Naoyuki; Furuichi, Tatsuya; Ikegawa, Shiro; Ohmura, Koichiro; Mimori, Tsuneyo; Matsuda, Fumihiko; Iwamoto, Takuji; Momohara, Shigeki; Yamanaka, Hisashi; Yamada, Ryo; Kubo, Michiaki; Nakamura, Yusuke; Yamamoto, Kazuhiko.

In: Nature Genetics, Vol. 42, No. 6, 01.06.2010, p. 515-519.

Research output: Contribution to journalArticle

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AU - Okada, Yukinori

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AU - Takahashi, Atsushi

AU - Yamazaki, Keiko

AU - Hosono, Naoya

AU - Myouzen, Keiko

AU - Tsunoda, Tatsuhiko

AU - Kamatani, Naoyuki

AU - Furuichi, Tatsuya

AU - Ikegawa, Shiro

AU - Ohmura, Koichiro

AU - Mimori, Tsuneyo

AU - Matsuda, Fumihiko

AU - Iwamoto, Takuji

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AU - Yamanaka, Hisashi

AU - Yamada, Ryo

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

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N2 - Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here, through a genome-wide association study of rheumatoid arthritis, we identified a polymorphism in CCR6, the gene encoding chemokine (C-C motif) receptor 6 (a surface marker for Th17 cells) at 6q27, that was associated with rheumatoid arthritis susceptibility and was validated in two independent replication cohorts from Japan (rs3093024, a total of 7,069 individuals with rheumatoid arthritis (cases) and 20,727 controls, overall odds ratio = 1.19, P = 7.7 × 10-19). We identified a triallelic dinucleotide polymorphism of CCR6 (CCR6DNP) in strong linkage disequilibrium with rs3093024 that showed effects on gene transcription. The CCR6DNP genotype was correlated with the expression level of CCR6 and was associated with the presence of interleukin-17 (IL-17) in the sera of subjects with rheumatoid arthritis. Moreover, CCR6DNP was associated with susceptibility to Graves' and Crohn's diseases. These results suggest that CCR6 is critically involved in IL-17-driven autoimmunity in human diseases.

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Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A et al. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nature Genetics. 2010 Jun 1;42(6):515-519. https://doi.org/10.1038/ng.583