Details

Autor(en) / Beteiligte

• Ikegawa, Shiro
• Miyamoto, Yoshinari
• Shi, Dongquan
• Nakajima, Masahiro
• Ozaki, Kouichi
• Sudo, Akihiro
• Kotani, Akihiro
• Uchida, Atsumasa
• Tanaka, Toshihiro
• Fukui, Naoshi
• Tsunoda, Tatsuhiko
• Takahashi, Atsushi
• Nakamura, Yusuke
• Jiang, Qing

Titel

Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis

Ist Teil von

• Nature genetics, 2008-08, Vol.40 (8), p.994-998

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Susceptibility to osteoarthritis, the most common human arthritis, is known to be influenced by genetic factors. Through a genome-wide association study using ∼100,000 SNPs, we have identified a previously unknown gene on chromosome 3p24.3, DVWA, which is associated with susceptibility to knee osteoarthritis. Expressed specifically in cartilage, DVWA encodes a 276-amino-acid protein with two regions corresponding to the von Willebrand factor type A domain (VWA domain). Several DVWA SNPs are significantly associated with knee osteoarthritis in two independent Japanese case-control cohorts. This association was replicated in a Japanese population cohort and a Han Chinese case-control cohort (combined P = 7.3 × 10−11). DVWA protein binds to β-tubulin, and the binding is influenced by two highly associated missense SNPs (rs11718863 and rs7639618) located in the VWA domain. The Tyr169-Cys260 isoform of DVWA, which is overrepresented in knee osteoarthritis, showed weaker interaction. Our findings reveal a new paradigm for study of osteoarthritis etiology and pathogenesis.