Abstract
Osteoarthritis (OA) is the most common cause of arthritis and represents an enormous healthcare burden in industrialized societies. Current therapeutic approaches for OA are limited and are insufficient to prevent the initiation and progression of the disease. Genetic studies of patients with OA can help to unravel the molecular mechanisms responsible for specific disease manifestations, including joint damage, nociception and chronic pain. Indeed, these studies have identified molecules, such as growth/differentiation factor 5, involved in signaling cascades that are important for the pathology of joint components. Genome-wide association studies have uncovered a likely role in OA for the genes encoding structural extracellular matrix components (such as DVWA) and molecules involved in prostaglandin metabolism (such as DQB1 and BTNL2). A ∼300 kilobase region in chromosome 7q22 is also associated with OA susceptibility. Finally, the identification of individuals at a high risk of OA and of total joint arthroplasty failure might be facilitated by the use of combinations of genetic markers, allowing for the application of preventive and disease-management strategies.
Key Points
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Severe osteoarthritis (OA) is a cause of social, economic and personal burden and is the main cause of an increasing need for joint replacements
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Candidate gene studies and genome-wide association studies show that OA is genetically heterogeneous with each individual common gene variant contributing only modestly to the risk of OA
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Genetic studies in humans have identified molecules that are important in the development of pathological changes to articular cartilage
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The genes involved in the main clinical end points of OA, such as chronic pain and functional disability, has not yet been studied extensively
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Preliminary studies suggest that it might be possible to combine sets of genetic variants to predict which individuals will be at a higher risk of OA
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Acknowledgements
This work was supported by European Commission Framework Program 7 grant 200800 TREAT-OA. T. D. Spector is an NIHR Senior Investigator.
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A. M. Valdes researched the data for the article and wrote the article. A. M. Valdes and T. D. Spector provided a substantial contribution to discussions of the content and to the review and/or editing of the manuscript before submission.
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Valdes, A., Spector, T. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol 7, 23–32 (2011). https://doi.org/10.1038/nrrheum.2010.191
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DOI: https://doi.org/10.1038/nrrheum.2010.191
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