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Title[redir]:
A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility | Nature Genetics
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
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arthritis, rheumatoid, google, scholar, nature, genet, association, japan, nat, ccr, cells, study, access, data, article, susceptibility, disease, genomewide, risk, japanese, population, laboratory, analyzed, content, analysis, genetics, diseases, med, riken, tokyo, cookies, kochi, okada, yamamoto, autoimmune, gene, chemokine, functional, studies, university, research, medicine, cgm, yokohama, privacy, suzuki, genetic, polymorphism, encoding, replication,
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nature portfolio permissions reprints privacy policy ifn-gamma-producing γδ effector advertising allied research basic research tnf-α-stimulated thp-1 cells nature 423 nature 447 nature 449 nature genome-wide association studies social media genotyping development genome-wide association defines genetic-based association studies genome-wide association study population-based association studies author correspondence springerlink instant access nf-κb family nonsynonymous single-nucleotide polymorphism population-based linkage analyses permissions ccr6-expressing th17 cells european economic area biobank japan project human genome center fourth control cohort privacy rheumatoid arthritis association th17 cells predominate competing financial interests article kochi human th17 cells complex genetic etiology incorporating genetic networks single nucleotide polymorphism strong linkage disequilibrium common autoimmune disease explore content subscription content joint autoimmune inflammation germinal center-related rheumatoid arthritis networking institutional subscriptions read ccr5 mark subsets systemic lupus erythematosus il12/il23 pathway
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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 Ã 10â19). 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-17âdriven autoimmunity in human diseases.
datePublished:2010-05-09T00:00:00Z
dateModified:2010-05-09T00:00:00Z
pageStart:515
pageEnd:519
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Gene regulation
Genetic predisposition to disease
Genome-wide association studies
Rheumatoid arthritis
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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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 Ã 10â19). 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-17âdriven autoimmunity in human diseases.
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Gene regulation
Genetic predisposition to disease
Genome-wide association studies
Rheumatoid arthritis
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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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:
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affiliation:
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address:
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type:PostalAddress
type:Organization
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affiliation:
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address:
name:Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan
type:PostalAddress
type:Organization
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
type:PostalAddress
type:Organization
name:Tatsuhiko Tsunoda
affiliation:
name:Laboratory for Medical Informatics, CGM, RIKEN
address:
name:Laboratory for Medical Informatics, CGM, RIKEN, Yokohama, Japan
type:PostalAddress
type:Organization
name:Naoyuki Kamatani
affiliation:
name:Laboratory for Statistical Analysis, CGM, RIKEN
address:
name:Laboratory for Statistical Analysis, CGM, RIKEN, Yokohama, Japan
type:PostalAddress
type:Organization
name:Tatsuya Furuichi
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: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
type:Organization
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:
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address:
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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:
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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
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
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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
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