Genetics of digital osteoarthritis

Joint Bone Spine. 2011 Jul;78(4):347-51. doi: 10.1016/j.jbspin.2010.09.012. Epub 2010 Oct 23.


Genetic factors contribute to the development of digital osteoarthritis, whose heritability has been estimated at 48 to 65%. Among the manifestations of digital osteoarthritis, only Heberden's nodes are transmitted by Mendelian inheritance, as a dominant trait in women and a recessive trait in men. The other forms of digital osteoarthritis are multifactorial, with a major gene and a residual multifactorial component that probably interacts with environmental factors. Hindrances to molecular studies include the absence to date of a universally accepted definition of the phenotype and the late onset of the manifestations. Genetic association studies of selected class I and II HLA genes produced conflicting results. The T303M polymorphism of the MATN3 gene, which was initially described as associated with hand osteoarthritis, may be more closely linked to trapeziometacarpal osteoarthritis than to digital osteoarthritis. Genome-wide scans have identified numerous loci linked to digital osteoarthritis. Replication has been achieved for some of these loci, most notably those located at 2p, 2q, 3p, 4q, and 7p. A recently published genome-wide association study showed that an A2BP1 gene polymorphism was significantly associated with hand osteoarthritis. Many candidate-gene studies found associations with AGC1, ASPN, ENPP1, HFE, KL, VDR, IL-1 cluster, and IL-6, although the results were not consistently reproducible. In one study, women with hand osteoarthritis had significant telomere shortening. Telomere shortening has also been reported in other age-related conditions.

Publication types

  • Review

MeSH terms

  • Female
  • Finger Joint / pathology*
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Osteoarthritis / genetics*
  • Osteoarthritis / pathology*
  • Polymorphism, Genetic
  • RNA Splicing Factors
  • RNA-Binding Proteins / genetics
  • Telomere Shortening


  • RBFOX1 protein, human
  • RNA Splicing Factors
  • RNA-Binding Proteins