The Increasing Complexity of Mercaptopurine Pharmacogenomics

Thiopurine methyltransferase (TPMT) activity shows significant interindividual variation, with approximately 90% of individuals having high (wild‐type) activity, 10% with intermediate activity, and 0.3% with low activity. Low and intermediate TPMT activity leads to toxicity from mercaptopurine and the need for dose reduction. Common variants in the TPMT gene have a strong association with mercaptopurine toxicity. However, recent research has shown that genetic contribution to mercaptopurine toxicity is more complex, possibly involving other genes, in particular ITPA , which encodes inosine triphosphate pyrophosphatase. Clinical Pharmacology & Therapeutics (2009); 85 , 2, 139–141 doi: 10.1038/clpt.2008.219