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         headline:A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility
         description:Yuta Kochi and colleagues identify a regulatory variant in CCR6 associated with susceptibility to rheumatoid arthritis. CCR6 encodes a chemokine receptor expressed on a subset of helper T cells known as Th17 cells, suggesting a possible role for CCR6 in Th17-driven autoimmunity. 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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      headline:A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility
      description:Yuta Kochi and colleagues identify a regulatory variant in CCR6 associated with susceptibility to rheumatoid arthritis. CCR6 encodes a chemokine receptor expressed on a subset of helper T cells known as Th17 cells, suggesting a possible role for CCR6 in Th17-driven autoimmunity. 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.
      datePublished:2010-05-09T00:00:00Z
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         Cancer Research
         Agriculture
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         name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
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      name:Kyoto University Graduate School of Medicine
      address:
         name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
         type:PostalAddress
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      address:
         name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Genotyping Development, CGM, RIKEN
      address:
         name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Genotyping Development, CGM, RIKEN
      address:
         name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
      address:
         name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Medical Informatics, CGM, RIKEN
      address:
         name:Laboratory for Medical Informatics, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Statistical Analysis, CGM, RIKEN
      address:
         name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Bone and Joint Diseases, CGM, RIKEN
      address:
         name:Laboratory for Bone and Joint Diseases, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory for Bone and Joint Diseases, CGM, RIKEN
      address:
         name:Laboratory for Bone and Joint Diseases, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Kyoto University Graduate School of Medicine
      address:
         name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
         type:PostalAddress
      name:Kyoto University Graduate School of Medicine
      address:
         name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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      name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine
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         name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
         type:PostalAddress
      name:Institute of Rheumatology, Tokyo Women's Medical University
      address:
         name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
         type:PostalAddress
      name:Institute of Rheumatology, Tokyo Women's Medical University
      address:
         name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
         type:PostalAddress
      name:Institute of Rheumatology, Tokyo Women's Medical University
      address:
         name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
         type:PostalAddress
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
      address:
         name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine
      address:
         name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
         type:PostalAddress
      name:Laboratory for Genotyping Development, CGM, RIKEN
      address:
         name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
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      address:
         name:Laboratory for International Alliance, CGM, RIKEN, Yokohama, Japan
         type:PostalAddress
      name:Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
      address:
         name:Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
         type:PostalAddress
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
      address:
         name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
         type:PostalAddress
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         name:Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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      name:Yuta Kochi
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            name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
            address:
               name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Yukinori Okada
      affiliation:
            name:Laboratory for Statistical Analysis, CGM, RIKEN
            address:
               name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Graduate School of Medicine, University of Tokyo
            address:
               name:Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Akari Suzuki
      affiliation:
            name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
            address:
               name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
      name:Katsunori Ikari
      affiliation:
            name:Institute of Rheumatology, Tokyo Women's Medical University
            address:
               name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Chikashi Terao
      affiliation:
            name:Kyoto University Graduate School of Medicine
            address:
               name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
               type:PostalAddress
            type:Organization
      name:Atsushi Takahashi
      affiliation:
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            address:
               name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
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      affiliation:
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            address:
               name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
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      affiliation:
            name:Laboratory for Genotyping Development, CGM, RIKEN
            address:
               name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
               type:PostalAddress
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      name:Keiko Myouzen
      affiliation:
            name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
            address:
               name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
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      affiliation:
            name:Laboratory for Medical Informatics, CGM, RIKEN
            address:
               name:Laboratory for Medical Informatics, CGM, RIKEN, Yokohama, Japan
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            type:Organization
      name:Naoyuki Kamatani
      affiliation:
            name:Laboratory for Statistical Analysis, CGM, RIKEN
            address:
               name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
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            type:Organization
      name:Tatsuya Furuichi
      affiliation:
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            address:
               name:Laboratory for Bone and Joint Diseases, CGM, RIKEN, Yokohama, Japan
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            type:Organization
      name:Shiro Ikegawa
      affiliation:
            name:Laboratory for Bone and Joint Diseases, CGM, RIKEN
            address:
               name:Laboratory for Bone and Joint Diseases, CGM, RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
      name:Koichiro Ohmura
      affiliation:
            name:Kyoto University Graduate School of Medicine
            address:
               name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
               type:PostalAddress
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      name:Tsuneyo Mimori
      affiliation:
            name:Kyoto University Graduate School of Medicine
            address:
               name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
               type:PostalAddress
            type:Organization
      name:Fumihiko Matsuda
      affiliation:
            name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine
            address:
               name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
               type:PostalAddress
            type:Organization
      name:Takuji Iwamoto
      affiliation:
            name:Institute of Rheumatology, Tokyo Women's Medical University
            address:
               name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Shigeki Momohara
      affiliation:
            name:Institute of Rheumatology, Tokyo Women's Medical University
            address:
               name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Hisashi Yamanaka
      affiliation:
            name:Institute of Rheumatology, Tokyo Women's Medical University
            address:
               name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Ryo Yamada
      affiliation:
            name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
            address:
               name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine
            address:
               name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
               type:PostalAddress
            type:Organization
      name:Michiaki Kubo
      affiliation:
            name:Laboratory for Genotyping Development, CGM, RIKEN
            address:
               name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
      name:Yusuke Nakamura
      affiliation:
            name:Laboratory for International Alliance, CGM, RIKEN
            address:
               name:Laboratory for International Alliance, CGM, RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo
            address:
               name:Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Kazuhiko Yamamoto
      affiliation:
            name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN
            address:
               name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Graduate School of Medicine, University of Tokyo
            address:
               name:Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
      name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
      name:Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
      name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
      name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
      name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
      name:Laboratory for Medical Informatics, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for Bone and Joint Diseases, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for Bone and Joint Diseases, CGM, RIKEN, Yokohama, Japan
      name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
      name:Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
      name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
      name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
      name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
      name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
      name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
      name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
      name:Laboratory for International Alliance, CGM, RIKEN, Yokohama, Japan
      name:Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
      name:Laboratory for Autoimmune Diseases, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan
      name:Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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