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New Genetic Marker for Osteoarthritis - Study Links Estrogen Receptor to Osteoarthritis in Both Men and Women
June 26, 2003Among patients with osteoarthritis (OA), a degenerative joint disease, postmenopausal women are the most prevalent. This fact has led to many hypotheses about the role of sex hormones in the cause and effects of OA.
Medical researchers at Erasmus MC in the Netherlands recently uncovered a compelling connection between a variation in gene for the estrogen receptor alpha and OA of the knee-in men as well as in women. Published in the July 2003 issue of Arthritis & Rheumatism, their study makes an important contribution to what could lead to early detection and treatment of OA, with the potential to spare many older patients the fate of disability. While affirming genetic influences as an important factor in the development of OA, this study calls for further research into the impact of estrogen on disease pathology.
The collaborative study of the departments of Internal Medicine and Epidemiology&Biostatistics focused on a large population-based sample of OA patients-1,483 in total-all Caucasian, all over the age of 55, and almost equally representing both genders. Each participant received radiographs of both knees to confirm disease presence and assess level of joint damage. To strengthen the radiographic evidence, two hallmarks of OA-joint space narrowing, due to cartilage loss, and osteophytosis, formation of bony outgrowths-were also evaluated. Each participant then received DNA tests to identify specific gene variants (or alleles) suspected of a role in OA, including the estrogen receptor alpha allele PX.
Among the study's participants, women carrying the allele PX gene had more than a two-fold increased risk for severe OA, determined by knee radiographs, compared with women without this estrogen receptor variant. What's more, the findings were similar for men.
The estrogen receptor alpha allele PX was also strongly associated with pronounced osteophytosis among participants of both sexes, but not joint space narrowing-even though estrogen receptors are found on cartilage as well as bone cells. "It has been suggested that estrogen exerts its protective effect on articular cartilage in particular," notes research team spokesperson Dr. Andre G. Uitterlinden, "but this finding suggests that bone metabolism plays a role. However, as ours is an 'association study' it does not establish 'cause and effect'. Therefore, the underlying mechanisms are still unclear and need further study."
Most significantly, this study reveals a new genetic marker for osteoarthritis, in both men and women. Estrogen, however, remains an intriguing risk factor in a disease afflicting the elderly in near epidemic proportions.
John Wiley & Sons
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