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

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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 languageEnglish
Pages (from-to)529-533
Number of pages5
JournalNature Genetics
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 2007

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Growth Differentiation Factor 5
5' Untranslated Regions
Osteoarthritis
Single Nucleotide Polymorphism
Population
Hip Osteoarthritis
Knee Osteoarthritis
Articular Cartilage
Genes
Arthritis
Epidemiologic Studies
Alleles

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Miyamoto, Y., Mabuchi, A., Shi, D., Kubo, T., Takatori, Y., Saito, S., ... Ikegawa, S. (2007). A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nature Genetics, 39(4), 529-533. https://doi.org/10.1038/2005

A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. / Miyamoto, Yoshinari; Mabuchi, Akihiko; Shi, Dongquan; Kubo, Toshikazu; Takatori, Yoshio; Saito, Susumu; Fujioka, Mikihiro; Sudo, Akihiro; Uchida, Atsumasa; Yamamoto, Seizo; Ozaki, Koichi; Takigawa, Masaharu; Tanaka, Toshihiro; Nakamura, Yusuke; Jiang, Qing; Ikegawa, Shiro.

In: Nature Genetics, Vol. 39, No. 4, 04.2007, p. 529-533.

Research output: Contribution to journalArticle

Miyamoto, Y, Mabuchi, A, Shi, D, Kubo, T, Takatori, Y, Saito, S, Fujioka, M, Sudo, A, Uchida, A, Yamamoto, S, Ozaki, K, Takigawa, M, Tanaka, T, Nakamura, Y, Jiang, Q & Ikegawa, S 2007, 'A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis', Nature Genetics, vol. 39, no. 4, pp. 529-533. https://doi.org/10.1038/2005
Miyamoto, Yoshinari ; Mabuchi, Akihiko ; Shi, Dongquan ; Kubo, Toshikazu ; Takatori, Yoshio ; Saito, Susumu ; Fujioka, Mikihiro ; Sudo, Akihiro ; Uchida, Atsumasa ; Yamamoto, Seizo ; Ozaki, Koichi ; Takigawa, Masaharu ; Tanaka, Toshihiro ; Nakamura, Yusuke ; Jiang, Qing ; Ikegawa, Shiro. / A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. In: Nature Genetics. 2007 ; Vol. 39, No. 4. pp. 529-533.
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