title: Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis.
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.
authors.affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Dongquan
authors.initials: D
authors.lastname: Shi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sudo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kotani
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Uchida
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D044466:Asian People / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D024142:Collagen Type VI; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D020370:Osteoarthritis, Knee / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011544:Pseudogenes
chemical_list: C531065:COL6A4P1 protein, human; D024142:Collagen Type VI; D011506:Proteins