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Typing TPMT and ITPase to detect azathioprine toxicity.

Genetic variation in thiopurine methyltransferase (TPMT) enzyme activity strongly predicts adverse effects in patients treated with the thiopurine drugs, azathioprine and 6-mercaptopurine, and is one of the classic examples of pharmacogenetics in clinical practice. Recently, polymorphic variation in the gene encoding the enzyme inosine triphosphatase (ITPase) has also been associated with risk of thiopurine-related toxicity. This article reviews the evidence for the role of TPMT and ITPase deficiency as predictors of thiopurine toxicity and makes recommendations for clinical and laboratory practice.