A Regulatory Variant in CCR6 is Associated with Rheumatoid Arthritis Susceptibility

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 May 11

PMID 20453841

Citations 123

Authors

Yuta Kochi

Yukinori Okada

Akari Suzuki

Katsunori Ikari

Chikashi Terao

Atsushi Takahashi

Keiko Yamazaki

Naoya Hosono

Keiko Myouzen

Tatsuhiko Tsunoda

Naoyuki Kamatani

Tatsuya Furuichi

Shiro Ikegawa

Koichiro Ohmura

Tsuneyo Mimori

Fumihiko Matsuda

Takuji Iwamoto

Shigeki Momohara

Hisashi Yamanaka

Ryo Yamada

Michiaki Kubo

Yusuke Nakamura

Kazuhiko Yamamoto

Affiliations

Soon will be listed here.

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.

Citing Articles

Inflammatory diseases causing joint and bone destruction: rheumatoid arthritis and hemophilic arthropathy.

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Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis.

Zhang M, Qin Z, Huang Y, Tian W, Li Y, Wang C J Transl Autoimmun. 2024; 8:100234.

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Increased gene expression of CCR6 and RORγt in peripheral blood cells of rheumatoid arthritis patients and their correlation with anti-cyclic citrullinated peptide and disease activity.

Roghani S, Lotfi R, Soroush M, Khorasanizadeh A, Feizollahi P, Assar S Immun Inflamm Dis. 2023; 11(12):e1112.

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A Review of the Occurrence of Rheumatoid Arthritis and Potential Treatments through Medicinal Plants from an Indian Perspective.

Shekh M, Ahmed N, Kumar V Curr Rheumatol Rev. 2023; 20(3):241-269.

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Association of IL-17F rs2397084 (E126G), rs11465553 (V155I) and rs763780 (H161R) variants with rheumatoid arthritis and their effects on the stability of protein.

Ali Y, Kausar M, Farooq M, Farooqi N, Islam Z, Khan S PLoS One. 2023; 18(9):e0285874.

PMID: 37751416 PMC: 10522029. DOI: 10.1371/journal.pone.0285874.

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