Scientists find new cause of gout

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In a study from the University of California San Diego and elsewhere, scientists found a new cause of gout.

They identified a novel molecular pathway that causes gout and its progression to joint tissue erosion.

The findings suggest lubricin, a protein found in joint fluid, as a novel therapeutic target for both the prevention and treatment of the disease.

Gout is the most common form of inflammatory arthritis, in which urate (a byproduct of purine-rich foods like meat and alcohol) builds up in the body and forms needle-shaped crystals in and around the joints, usually starting in the foot.

The crystal deposits lead to flares of severe pain, joint swelling and tenderness, and can progress to chronic joint damage that limits patients’ movement and quality of life.

Excess urate circulating in the blood (known as hyperuricemia) has long been considered the major cause of gout, but counterintuitively, most people with high urate levels do not actually develop the disease.

In fact, asymptomatic hyperuricemia is approximately four times more prevalent than gout.

Gout patients also show mysteriously higher levels of urate in their joint fluid compared to their blood.

In the study, the team was interested in exploring the genetic factors that lead not to high levels of circulating urate, but specifically to urate production and crystal deposition within joints.

To do this, they studied a rare case of gout in which the patient had developed urate crystal deposits and erosion in her joints but did not show high levels of urate in her blood.

The researchers were able to identify a major molecular pathway that was disrupted in the patient, centering on a significant reduction in lubricin.

The mucinous protein provides essential lubrication and protection to joint tissues and regulates the function of a specific type of white blood cell that promotes inflammation in the joint.

Additional experiments confirmed that under healthy conditions, lubricin suppresses the secretion of urate and xanthine oxidase (an enzyme that produces urate) by activating white blood cells, and also blocks urate from crystallizing in the joint.

The researchers then assessed several patients with the common form of gout and confirmed that they too had markedly decreased levels of lubricin.

The authors suggest that whether or not a hyperacemia patient goes on to develop gout may thus be influenced by which gene variants they have for lubricin and other molecules that control its production or degradation in the joint.

If you care about pain, please read studies about vitamins that could help reduce bone fracture risk, and gout drug may help treat heart failure.

For more information about wellness, please see recent studies that Krill oil could improve muscle health in older people, and blood pressure diet may help prevent gout flares.

The study was conducted by Robert Terkeltaub et al and published in Arthritis & Rheumatology.

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