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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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      address:
         name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
         type:PostalAddress
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         name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
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            address:
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            address:
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            address:
               name:Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
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      name:Takuji Iwamoto
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            name:Institute of Rheumatology, Tokyo Women's Medical University
            address:
               name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
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      name:Shigeki Momohara
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            address:
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               type:PostalAddress
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      name:Hisashi Yamanaka
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            name:Institute of Rheumatology, Tokyo Women's Medical University
            address:
               name:Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
               type:PostalAddress
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      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
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            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
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      affiliation:
            name:Laboratory for Genotyping Development, CGM, RIKEN
            address:
               name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
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      name:Yusuke Nakamura
      affiliation:
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            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
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      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
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