Genetic Variation Cuts Osteoarthritis Risk

by VR Sreeraman on  April 10, 2010 at 3:15 PM Research News
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 Genetic Variation Cuts Osteoarthritis Risk
A variant of a gene involved in the inflammatory process seems to stave off joint destruction caused by osteoarthritis, indicates research published ahead of print in the Annals of the Rheumatic Diseases.

The finding prompts the researchers to conclude that this variant might also affect an individual's responsiveness to drugs used to treat the disease.

Osteoarthritis is the most common of the degenerative joint diseases and a major cause of disability, particularly among the elderly.

Female gender, older age, excess weight and previous damage caused by injury are all known risk factors. But genes are also thought to have a role both in its initiation and progression.

The researchers assessed the genetic profiles of 531 people with late stage osteoarthritis of the knee or hip, severe enough to warrant replacement of the affected joint.

The 320 women and 211 men were all aged under 76 and had no other inflammatory diseases. Most (422) had primary osteoarthritis; the remainder had secondary disease, related to other factors, such as injury.

Their profiles were compared with those of 400 healthy blood donors.

The researchers were looking for a common variant (polymorphism) of the COX-2 gene promoter, known as rs20417. This gene is known to be involved in boosting the body's inflammatory response.

Each cell has two copies of a gene, known as alleles, both of which may have different coding sequences, referred to as letter combinations of C or G.

When the researchers looked at these alleles, they found that two thirds of the healthy blood donors had a G/G combination; just under a third (31%) had C/G; and 3% had C/C.

But among the patients with osteoarthritis, almost eight out of 10 (over 78%) had the G/G combination; one in five the C/G; and 1% the C/C combination.

When they compared these results, people with any combination containing a C code had a lower risk for end stage disease, irrespective of the joint involved.

On the other hand, test tube studies on cartilage cells (chondrocytes) indicated that a third of the samples with the G/G combination were strongly activated by an inflammatory protein (IL1 beta), suggesting an increased risk for joint degeneration.

The authors add that rs20417 has been associated with various other diseases in which inflammatory processes are involved. These include heart attack, stroke, Alzheimer's disease, rheumatoid arthritis and gum disease.

"The results of this study raise the hypothesis that rs20417 is associated with the initiation and/or progression of hip and knee [osteoarthritis]," they conclude.

They add that it "might also be related to the responses of patients with [osteoarthritis] to pharmacological treatment."

Source: BMJ

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