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Immunity gene predicts severe adverse drug reaction

DURHAM, N.C. -- In a study of Han Chinese patients, researchers have for the first time directly linked a gene of the immune system to a severe adverse drug reaction called Stevens-Johnson syndrome (SJS), according to a Duke University Medical Center medical geneticist and collaborators in Taiwan.

The sometimes fatal condition is characterized by a blistering rash that can lead to detachment of the skin and inflammation of the gastrointestinal and respiratory lining. More than 100 drugs -- including antibiotics, NSAIDS, anticonvulsants and the gout drug allopurinol -- are known to cause SJS in rare cases. The frequency with which particular prescriptions spur the devastating reaction varies among people of different ethnic backgrounds.

Their new test for the predisposing gene could be applied almost immediately to determine which of the 1.2 billion Chinese worldwide would be at risk for the reaction to the popular anti-epilepsy drug carbamazepine (trade name Tegretol), said Y-T Chen, M.D., chief of medical genetics at Duke University Medical Center and director of the Institute of Biomedical Sciences at Academia Sinica in Taiwan. The anticonvulsant is the most common cause of SJS among the Chinese population.

The finding highlights the promise of pharmacogenomics for avoiding drugs' most serious side effects and might also lead to advances in the clinical trial of new drugs, said the researchers.

A single genetic marker predicted with 100 percent accuracy those who could safely take carbamazepine, the team reported in the April 1, 2004, issue of Nature. Individuals with a particular version of the immunity gene who took the drug suffered the devastating reaction in all but 3 percent of the cases.

Whether the gene variant will predict the drug reaction in people of other ethnic backgrounds remains to be tested, said Chen. However, his team expects that other similar genes will be found to underlie the reaction induced by the ma
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-4148
Duke University Medical Center
1-Apr-2004


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