Mutation analysis of the Smad3 gene in human osteoarthritis

Eur J Hum Genet. 2003 Sep;11(9):714-7. doi: 10.1038/sj.ejhg.5201034.


Osteoarthritis (OA) is the most common joint disease worldwide. Recent studies have shown that targeted disruption of Smad3 in mouse results in OA. To reveal the possible association between the Smad3 gene mutation and human OA, we employed polymerase chain reaction-single strand conformation polymorphism and sequencing to screen mutations in all nine exons of the Smad3 gene in 32 patients with knee OA and 50 patients with only bone fracture. A missense mutation of the Smad3 gene was found in one patient. The single base mutation located in the linker region of the SMAD3 protein was A --> T change in the position 2 of codon 197 and resulted in an asparagine to isoleucine amino-acid substitution. The expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 in sera of the patient carrying the mutation were higher than other OA patients and controls. This is the first report showing that the Smad3 gene mutations could be associated with the pathogenesis of human OA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Electrophoresis
  • Gene Expression*
  • Humans
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 2 / genetics
  • Mutation, Missense / genetics
  • Osteoarthritis / genetics*
  • Polymorphism, Single-Stranded Conformational
  • Sequence Analysis, DNA
  • Smad3 Protein
  • Trans-Activators / genetics*


  • DNA-Binding Proteins
  • SMAD3 protein, human
  • Smad3 Protein
  • Trans-Activators
  • Matrix Metalloproteinase 2