1. A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis.
- Author
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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, and Ikegawa, Shiro
- Subjects
OSTEOARTHRITIS ,ARTICULAR cartilage diseases ,DISEASES in older people ,GROWTH factors ,GENETIC polymorphisms ,JAPANESE people ,DISEASES - 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. [ABSTRACT FROM AUTHOR]- Published
- 2007
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