Genetic Aspects of Osteoarthritis
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
References (23)
Genome studies and linkage in primary osteoarthritis
Rheum Dis Clin North Am
(2002)- et al.
Osteoarthritis in children associated with a mutation in the type II procollagen gene (COL2A1)
Mol Genet Metab
(2001) - et al.
Genetic markers of osteoarticular disordersfacts and hopes
Arthritis Res
(2001) Genetic epidemiology of primary osteoarthritis
Curr Opin Rheumatol
(2001)- et al.
Familial aggregation of osteoarthritisdata from the Baltimore Longitudinal Study on Aging
Arthritis Rheum
(1998) - et al.
Evidence for a Mendelian gene in a segregation analysis of generalized radiographic osteoarthritisthe Framingham Study
Arthritis Rheum
(1998) - et al.
Genetic influences on osteoarthritis in womena twin study
BMJ
(1996) - et al.
The genetic contribution to radiographic hip osteoarthritis in womenresults of a classic twin study
Arthritis Rheum
(2000) - et al.
Genetic influences on cervical and lumbar disc degenerationa magnetic resonance imaging study in twins
Arthritis Rheum
(1999) Collagen of articular cartilage
Arthritis Res
(2002)
Gycosylated matrix proteins
Cited by (11)
Cartilage in normal and osteoarthritis conditions
2008, Best Practice and Research: Clinical RheumatologyCitation 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.
Are bone losers distinguishable from bone formers in a skeletal series? Implications for adult age at death assessment methods
2007, HOMO- Journal of Comparative Human BiologyIdentification of novel genetic variations affecting osteoarthritis patients
2016, BMC Medical GeneticsThe effect of factors other than age upon skeletal age indicators in the adult
2015, Annals of Human Biology
Supported by grants from the National Health and Medical Research Council of Australia and the Murdoch Children’s Research Institute.