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

Nat Genet. 2008 Aug;40(8):994-8. doi: 10.1038/ng.176. Epub 2008 Jul 11.


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.

MeSH terms

  • Asian People / genetics
  • Chromosomes, Human, Pair 3 / genetics
  • Collagen Type VI
  • Genetic Predisposition to Disease*
  • Humans
  • Molecular Sequence Data
  • Osteoarthritis, Knee / genetics*
  • Proteins / genetics*
  • Pseudogenes


  • COL6A4P1 protein, human
  • Collagen Type VI
  • Proteins

Associated data

  • GENBANK/AB299979
  • OMIM/MIM165720
  • RefSeq/XM_497913