A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility.
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.
Kochi
Yuta
Y
Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan. ykochi@src.riken.jp
Okada
Yukinori
Y
Suzuki
Akari
A
Ikari
Katsunori
K
Terao
Chikashi
C
Takahashi
Atsushi
A
Yamazaki
Keiko
K
Hosono
Naoya
N
Myouzen
Keiko
K
Tsunoda
Tatsuhiko
T
Kamatani
Naoyuki
N
Furuichi
Tatsuya
T
Ikegawa
Shiro
S
Ohmura
Koichiro
K
Mimori
Tsuneyo
T
Matsuda
Fumihiko
F
Iwamoto
Takuji
T
Momohara
Shigeki
S
Yamanaka
Hisashi
H
Yamada
Ryo
R
Kubo
Michiaki
M
Nakamura
Yusuke
Y
Yamamoto
Kazuhiko
K
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
C106311:CCR6 protein, human; D020381:Interleukin-17; D054399:Receptors, CCR6
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