TY - JOUR
T1 - A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility
AU - Kochi, Yuta
AU - Okada, Yukinori
AU - Suzuki, Akari
AU - Ikari, Katsunori
AU - Terao, Chikashi
AU - Takahashi, Atsushi
AU - Yamazaki, Keiko
AU - Hosono, Naoya
AU - Myouzen, Keiko
AU - Tsunoda, Tatsuhiko
AU - Kamatani, Naoyuki
AU - Furuichi, Tatsuya
AU - Ikegawa, Shiro
AU - Ohmura, Koichiro
AU - Mimori, Tsuneyo
AU - Matsuda, Fumihiko
AU - Iwamoto, Takuji
AU - Momohara, Shigeki
AU - Yamanaka, Hisashi
AU - Yamada, Ryo
AU - Kubo, Michiaki
AU - Nakamura, Yusuke
AU - Yamamoto, Kazuhiko
N1 - Funding Information:
thank the members of BioBank Japan and the Rotary Club of Osaka-Midosuji District 2660 Rotary International for supporting our study. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Sciences and Technology of the Japanese government. The replication study of rheumatoid arthritis was performed under the support of Genetics and Allied research in Rheumatoid Arthritis Networking (GARNET) consortium.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77952885768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952885768&partnerID=8YFLogxK
U2 - 10.1038/ng.583
DO - 10.1038/ng.583
M3 - Article
C2 - 20453841
AN - SCOPUS:77952885768
SN - 1061-4036
VL - 42
SP - 515
EP - 519
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -
