Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis |
| |
Authors: | 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 Ikegawa Shiro |
| |
Institution: | Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. |
| |
Abstract: | Susceptibility to osteoarthritis, the most common human arthritis, is known to be influenced by genetic factors. Through a genome-wide association study using approximately 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 x 10(-11)). DVWA protein binds to beta-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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|