Genetic Aspects of Osteoarthritis

https://doi.org/10.1016/j.semarthrit.2004.03.006Get rights and content

Section snippets

Genetic Studies

Early family studies suggested that OA showed familial clustering, and were followed by several epidemiologic studies on unselected populations, the Baltimore Longitudinal Study of Aging and the Framington Offspring Study, both of which confirmed familial clustering of hand and knee OA (4, 5). Samples from these studies have been used in candidate gene approaches to identify OA susceptibility genes (see below). Twin studies have been particularly useful in further defining the genetic nature of

Genome-wide Linkage Studies

Genome-wide linkage analysis uses unique gene sequences, such as microsatellite markers or defined-gene single-nucleotide polymorphisms (SNPs), to scan the entire genome to look for the linkage of these markers to the disease phenotype in family pedigrees in which inheritance is apparent, as well as in affected sibling pairs. By detection of the linkage to these high-density markers, the chromosomal region(s) containing the disease gene(s) are defined. These loci usually contain many genes,

Candidate Gene Studies

Another approach to OA gene mutation characterization is the study of possible candidate genes in the family pedigrees using case-control cohorts. The candidate genes that have been targeted for study are predominantly those encoding the structural ECM proteins of cartilage and bone, and genes involved in cartilage and bone growth and maturation. Although association and linkage studies are a powerful approach to either include or exclude genes as disease-causing, they are restricted by the

The Collagen II Arg519Cys Mutation and OA

Linkage and association data exclude cartilage type II collagen as a common cause of idiopathic OA. However, collagen II clearly is involved in some cases. As discussed earlier, the relatively rare sporadic dominant-negative mutations of collagen II cause severe chondrodysplasias, a component of which involves joint abnormalities and dysfunction that would lead to OA if normal growth and ambulation were possible in these disorders (12). Furthermore, collagen II mutations cause premature OA in

Conclusions

It is clear that genetic factors are among the important risk factors in OA. Although the precise definition of the genes involved in susceptibility to OA has not been comprehensively achieved, recent advances in high-throughput genomics, gene-expression profiling, and proteomics heralds a new era that promises to rapidly define the molecular mechanisms of OA and other complex disease processes. The obvious candidates, such as cartilage ECM components and regulatory factors, might play a role

First page preview

First page preview
Click to open first page preview

References (23)

  • J. Loughlin

    Genome studies and linkage in primary osteoarthritis

    Rheum Dis Clin North Am

    (2002)
  • R.J. Mier et al.

    Osteoarthritis in children associated with a mutation in the type II procollagen gene (COL2A1)

    Mol Genet Metab

    (2001)
  • M.L. Brandi et al.

    Genetic markers of osteoarticular disordersfacts and hopes

    Arthritis Res

    (2001)
  • J. Loughlin

    Genetic epidemiology of primary osteoarthritis

    Curr Opin Rheumatol

    (2001)
  • R. Hirsch et al.

    Familial aggregation of osteoarthritisdata from the Baltimore Longitudinal Study on Aging

    Arthritis Rheum

    (1998)
  • D.T. Felson et al.

    Evidence for a Mendelian gene in a segregation analysis of generalized radiographic osteoarthritisthe Framingham Study

    Arthritis Rheum

    (1998)
  • T.D. Spector et al.

    Genetic influences on osteoarthritis in womena twin study

    BMJ

    (1996)
  • A.J. MacGregor et al.

    The genetic contribution to radiographic hip osteoarthritis in womenresults of a classic twin study

    Arthritis Rheum

    (2000)
  • P.N. Sambrook et al.

    Genetic influences on cervical and lumbar disc degenerationa magnetic resonance imaging study in twins

    Arthritis Rheum

    (1999)
  • D. Eyre

    Collagen of articular cartilage

    Arthritis Res

    (2002)
  • D. Heinegard et al.

    Gycosylated matrix proteins

  • Cited by (11)

    • Cartilage in normal and osteoarthritis conditions

      2008, Best Practice and Research: Clinical Rheumatology
      Citation Excerpt :

      All the proteases involved in collagen fibril degradation can be expressed by the chondrocytes. Genetic studies have also indicated that the COL2A1, COL9A1, and COL11A2 genes might represent susceptibility genes that predispose to articular cartilage degeneration in some cases of primary idiopathic OA.20 Cartilage is characterized by its high content of aggrecan, which exists in association with HA and link protein in the form of proteoglycan aggregates that provide the osmotic properties needed for articular cartilage to resist compressive loads.

    View all citing articles on Scopus

    Supported by grants from the National Health and Medical Research Council of Australia and the Murdoch Children’s Research Institute.

    View full text