A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis

Nat Genet. 2007 Apr;39(4):529-33. doi: 10.1038/2005. Epub 2007 Mar 25.


Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.

Publication types

  • Multicenter Study

MeSH terms

  • 5' Untranslated Regions*
  • Asian People / genetics
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / physiology
  • Case-Control Studies
  • Cells, Cultured
  • Gene Expression Regulation
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Growth Differentiation Factor 5
  • Humans
  • Linkage Disequilibrium
  • Osteoarthritis / genetics*
  • Polymorphism, Single Nucleotide* / physiology
  • Transfection


  • 5' Untranslated Regions
  • Bone Morphogenetic Proteins
  • GDF5 protein, human
  • Growth Differentiation Factor 5

Associated data

  • RefSeq/NM_000557