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Gene Variant Reduces Risk of Joint Damage in Osteoarthritis

COX-2 gene promoter variant tied to lower risk for end-stage hip, knee OA; another variant may up risk

THURSDAY, April 22 (HealthDay News) -- Having a certain variant of a gene involved in the inflammatory process may ward off joint destruction resulting from osteoarthritis (OA) in the hip and knee, though another variant is associated with an increased risk of joint destruction, according to a study published online April 8 in the Annals of the Rheumatic Diseases.

E. Marion Schneider, M.D., of the University Hospital Ulm in Germany, and colleagues genotyped the single nucleotide polymorphism −765 G→C (rs20417) of the COX-2 gene promoter in a population of 531 patients who had OA of the knee or hip severe enough to warrant joint replacement. The researchers also genotyped a control group of 400 healthy subjects.

The researchers found that 66 percent of the healthy subjects had alleles with G/G coding sequence, 31 percent had C/G, and 3 percent had C/C. Among the OA patients, 78.4 percent had G/G coding sequence, 20.5 percent had C/G, and 1.1 percent had C/C. Comparing the results, the researchers found a lower risk of end-stage OA for subjects with a coding sequence containing C (per allele odds ratio, 0.57). However, a third of the samples with the G/G combination were strongly activated by an inflammatory protein (IL1β), indicating increased joint degeneration risk.

"The results of this study raise the hypothesis that rs20417 is associated with the initiation and/or progression of hip and knee OA. This observation needs to be confirmed in independent patient cohorts. If subsequent studies confirm a functional impact on the expression of COX-2 and prostaglandin synthesis, this polymorphism might also be related to the responses of patients with OA to pharmacological treatment," the authors write.

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