A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis

Yoshinari Miyamoto; Akihiko Mabuchi; Dongquan Shi; Toshikazu Kubo; Yoshio Takatori; Susumu Saito; Mikihiro Fujioka; Akihiro Sudo; Atsumasa Uchida; Seizo Yamamoto; Koichi Ozaki; Masaharu Takigawa; Toshihiro Tanaka; Yusuke Nakamura; Qing Jiang; Shiro Ikegawa

doi:10.1038/2005

A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis

Yoshinari Miyamoto, Akihiko Mabuchi, Dongquan Shi, Toshikazu Kubo, Yoshio Takatori, Susumu Saito, Mikihiro Fujioka, Akihiro Sudo, Atsumasa Uchida, Seizo Yamamoto, Koichi Ozaki, Masaharu Takigawa, Toshihiro Tanaka, Yusuke Nakamura, Qing Jiang, Shiro Ikegawa

Dental School

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Abstract

Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5′ UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 × 10^-13) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.

Original language	English
Pages (from-to)	529-533
Number of pages	5
Journal	Nature Genetics
Volume	39
Issue number	4
DOIs	https://doi.org/10.1038/2005
Publication status	Published - Apr 2007

ASJC Scopus subject areas

Genetics

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10.1038/2005

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title = "A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis",

abstract = "Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5′ UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 × 10-13) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.",

author = "Yoshinari Miyamoto and Akihiko Mabuchi and Dongquan Shi and Toshikazu Kubo and Yoshio Takatori and Susumu Saito and Mikihiro Fujioka and Akihiro Sudo and Atsumasa Uchida and Seizo Yamamoto and Koichi Ozaki and Masaharu Takigawa and Toshihiro Tanaka and Yusuke Nakamura and Qing Jiang and Shiro Ikegawa",

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AU - Miyamoto, Yoshinari

AU - Mabuchi, Akihiko

AU - Shi, Dongquan

AU - Kubo, Toshikazu

AU - Takatori, Yoshio

AU - Saito, Susumu

AU - Fujioka, Mikihiro

AU - Sudo, Akihiro

AU - Uchida, Atsumasa

AU - Yamamoto, Seizo

AU - Ozaki, Koichi

AU - Takigawa, Masaharu

AU - Tanaka, Toshihiro

AU - Nakamura, Yusuke

AU - Jiang, Qing

AU - Ikegawa, Shiro

PY - 2007/4

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N2 - Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5′ UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 × 10-13) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.

AB - Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5′ UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 × 10-13) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.

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A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis

Abstract

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