title: A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.
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 x 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.
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan. ykochi@src.riken.jp
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Keiko
authors.initials: K
authors.lastname: Myouzen
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Furuichi
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020381:Interleukin-17 / Q000097:blood; D011110:Polymorphism, Genetic; D054399:Receptors, CCR6 / Q000235:genetics* / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional
chemical_list: C106311:CCR6 protein, human; D020381:Interleukin-17; D054399:Receptors, CCR6
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