05/12/2010 - Articles

Gene variant linked to osteoarthritis

By: Susan Aldridge, medical journalist, PhD


Osteoarthritis is the most common of the degenerative joint diseases and it is a significant cause of disability among older people. We know that age, overweight and obesity, as well as a history of injury, are risk factors for osteoarthritis. But genetic factors are involved as well. Researchers in Germany have now uncovered a variant in a gene known as COX-2. We know that this gene is involved in the inflammatory process which appears to be involved in end-stage hip and knee osteoarthritis. The variant involves a change in the DNA of this gene from coding letter G to C. Note that the genetic code of DNA is ‘written’ in chemicals called four bases known as G, C, A and T for short and in gene variants, these letters are swapped and substituted in various places on the genome.  Also, each person bears two copies – known as alleles – of each gene. One is inherited from the mother, one from the father.

In this study, the researchers assessed the genetic profiles of 531 people (320 women, 211 men) with end-stage osteoarthritis of the knee or hip. All were candidates for joint replacement. The profiles were compared to those of 400 healthy blood donors. Two thirds of the blood donors had two G alleles of COX-2, just under a third had one C and one G, while only 3% had two C alleles. When it came to the participants with osteoarthritis, the pattern was quite different. Eight out of ten had two G alleles, one in five had one C and one G and 1% had two C alleles. In other words, having a C allele of COX-2 was linked to lower risk of osteoarthritis. And test tube studies on cartilage cells showed that one third of samples with a G, G combination were strongly activated by an inflammatory protein, which would set the scene for joint degeneration. The researchers note that this gene has been linked with other inflammatory diseases and wonder if the harmful gene variant might mean that individuals with osteoarthritis are less likely to respond to anti-inflammatory drugs. The findings open a new window on our understanding of osteoarthritis and may, in time, help find more effective treatment.



Schneider EM et al The (-765 G to C) promoter variant of the COX-2/PTGS2 gene is associated with a lower risk for end-stage hip and knee osteoarthritis Online First Annals of Rheumatic Diseases 2010; doi 10.1136/and 2009.124040


Created on: 05/12/2010
Reviewed on: 05/12/2010

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