Details

Autor(en) / Beteiligte

• Ikegawa, Shiro
• 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

Titel

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

Ist Teil von

• Nature genetics, 2007-04, Vol.39 (4), p.529-533

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.