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The Increasing Complexity of Mercaptopurine Pharmacogenomics
Author(s) -
Marsh S,
Van Booven DJ
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2008.219
Subject(s) - pharmacogenomics , mercaptopurine , computational biology , biopharmaceutics , pharmacology , medicine , biology , genetics , pharmacognosy , biological activity , in vitro
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