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Leeds medics solve an ancient riddle -- and offer new tool for diagnosis
Date:5/30/2008

fatty compound called PGE2, which is produced naturally by the body to mediate the effects of internal inflammation. Crucially, once it has done its work, PGE2 is broken down by an enzyme 15-HPGD, produced in the lungs. The patients followed by the Leeds study were found to have a genetic mutation which prevented the production of 15-HPGD, reulting in up to ten times as much of the PGE2 in their systems.

"If you don't have this enzyme the PGE2 isn't broken down normally and simply builds up," said Bonthron, whose findings are published online this week in Nature Genetics.

In lung cancer patients, it is most likely overproduction of PGE2 by the tumour that causes the clubbing. In congenital heart disease, blood bypasses the lungs, where PGE2 is normally broken down by 15-HPGD.

The researchers have suggested that a straightforward urine test for levels of PGE2 may be a useful first step in the diagnosis of individuals with unexplained clubbing, and to understanding whether it is the symptom of something far more serious. The results also suggest that existing drugs such as aspirin, which are already used to prevent PGE2 production, may be effective in reducing the painful symptoms of finger clubbing.

It has taken 2,000 years to make the connection, but Bonthron adds: "Actually, when you look back, it's rather obvious. When we found this gene, everything else fell neatly into place it was like a smack on the forehead."


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Contact: Simon Jenkins
S.Jenkins@leeds.ac.uk
44-011-334-34031
University of Leeds
Source:Eurekalert  

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