COMMENTARY

Exploring the Genetic Link to Premature Osteoarthritis

Kevin Deane, MD

Disclosures

June 09, 2010

Premature Arthritis Is a Distinct Type II Collagen Phenotype

Kannu P, Bateman JF, Randle S, et al
Arthritis Rheum. 2010;62:1421-1430

Introduction

Osteoarthritis (OA) is extremely common, leading to significant morbidity. Some forms of OA are more severe -- presenting earlier in life and affecting a significant number of joints -- although even more mild forms of the disease can be substantially disabling. Identification of genetic factors that predispose to disease may help identify patients who will benefit from strategies protective against worsening joint disease, as well as help us understand biological pathways that lead to OA.

Study Summary

These investigators identified 2 families in Australia (Caucasians) whose members were affected before the age of 30 years with OA of the spine and large and small joints but without obvious extra-articular manifestations of a cartilage disorder. Of note, there are known genetic disorders of type II collagen, including spondyloepiphyseal dysplasia and Kniest dysplasia, that lead to distinct OA phenotypes; some disorders, including the Stickler syndrome, may also include extra-articular changes, including facial feature changes (small jaw, cleft palate, or other skull morphologic changes) and ocular disease.[1,2] However, these authors wanted to investigate premature OA that did not have significant extra-articular features to determine the role of type II collagen-related genetic factors in what is perhaps more mild disease. Genetic studies of these Australian families revealed sequence changes in the gene encoding type II collagen (COL2A1), resulting in glycine substitutions in the triple helical domain of type II collagen, likely leading to premature breakdown. Of interest, in these 2 families, patients with OA had HLA-B27 positivity, although the authors were not sure of the implications of this finding because of the absence of ankylosis of joints. Also, 1 of the patients seemed to improve with immunomodulatory therapy (corticosteroids and methotrexate). The authors conclude that type II collagen genetic disorders are related to forms of OA that lack significant extra-articular features, and they hypothesize that early identification of such risk may allow for better understanding of the natural history of disease, as well as implementation of prevention strategies in individuals with these genetic risk factors.

Viewpoint

Given the significant worldwide morbidity from OA, understanding the genetic and environmental factors that lead to disease is extremely important. We already know about some of the other type II collagen disorders that have a genetic basis, such as the Stickler syndrome and Kniest dysplasia, but these disorders are rare. Of interest here is the finding of genetic factors of type II collagen that are related to premature yet joint-limited OA. Certainly we need to learn more about the relationship between genetic and environmental factors that lead to even more mild (and far more common) forms of OA, but this study does provide data that type II collagen disorders may be related to a broader spectrum of OA. Also of interest was the apparent improvement in 1 patient with immunosuppression, suggesting (although not proving) that part of the disease process in these type II collagen disorders may be amenable to immunomodulation. Hopefully, these and future findings will lead to rational prevention strategies for OA.

Comments

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