Thiopurine Methyltransferase Genotype Predicts Therapy-Limiting Severe Toxicity from Azathioprine

Article Abstract:

Genetic testing may determine which patients taking azathioprine are likely to experience drug toxicity, limiting the usefulness of the drug. Azathioprine is used in the treatment of severe rheumatoid arthritis. Researchers analyzed 67 patients taking the drug to determine their genetic profile of a gene encoding thiopurine methyltransferase, an enyzme used in the breakdown of the drug. One profile was present in 5 of 6 patients who stopped taking the drug due to a low white blood cell count. Determining patients' thiopurine methyltransferase gene type before azathioprine therapy is begun may identify those likely to have a toxic response.

Complications and side effects, Drug therapy, Rheumatoid arthritis, Genetic polymorphisms

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Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance

Article Abstract:

Genetic analysis may identify individuals producing inadequate amounts of thiopurine S-methyltransferase (TPMT). TPMT-deficient individuals may experience life-threatening reactions to certain medications. Researchers measured TPMT activity in the blood of 282 persons and determined the DNA sequence for the TPMT gene in 21 persons with intermediate activity, a randomly selected group of 21 persons with high activity, and 6 persons with low activity. The six persons with low activity had two variant genes, 20 of the 21 with intermediate activity had one variant gene, and all 21 with high activity had two normal genes.

Measurement, Methyltransferases, Mercaptopurine

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Therapeutic lessons from pharmacogenetics

Article Abstract:

Genetic variability may have important effects on drug metabolism in that it may determine the dosage at which a drug is effective or toxic. For example, a study investigating the correspondence between the presence of a mutation in a gene coding for an enzyme and the production level of that enzyme explains why some persons treated with mercaptopurine or azathiopurine experience toxic reactions. Genetic variation is only one of many factors affecting drug metabolism. Nonetheless, in the future, genetic analysis may help physicians determine appropriate drug dosages.

Editorial

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