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. © 2008 Nature Publishing Group.
CITATION STYLE
Miyamoto, Y., Shi, D., Nakajima, M., Ozaki, K., Sudo, A., Kotani, A., … Ikegawa, S. (2008). Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis. Nature Genetics, 40(8), 994–998. https://doi.org/10.1038/ng.176
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