Letter abstract
Nature Genetics 40, 994 - 998 (2008)
Published online: 11 July 2008 | doi:10.1038/ng.176
Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis
Yoshinari Miyamoto1, Dongquan Shi2, Masahiro Nakajima1, Kouichi Ozaki3, Akihiro Sudo4, Akihiro Kotani5, Atsumasa Uchida4, Toshihiro Tanaka3, Naoshi Fukui6, Tatsuhiko Tsunoda7, Atsushi Takahashi8, Yusuke Nakamura9, Qing Jiang2 & Shiro Ikegawa1
Susceptibility to osteoarthritis, the most common human arthritis, is known to be influenced by genetic factors1, 2. 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)3. 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 
-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.
- Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Zhongshan Road 321, Nanjing 210008, Jiangsu, China.
- Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
- Department of Orthopaedic Surgery, Mie University Faculty of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
- Department of Orthopaedic Surgery, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
- Department of Pathomechanisms, Clinical Research Center for Rheumatology and Allergy, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Sagamihara 228-8522, Japan.
- The Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
- Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
- Laboratory for Genotyping, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Correspondence to: Shiro Ikegawa1 e-mail: sikegawa@ims.u-tokyo.ac.jp
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