Recent advances in the pharmacogenomics of thiopurine methyltransferase.

The thiopurine drugs (6-mercaptopurine, 6-thioguanine and azathioprine) are commonly used cytotoxic agents and immunosuppressants. One important route for the metabolism of these agents is methylation, mediated by thiopurine methyltransferase (TPMT). It is now well established that inter-individual variation in sensitivity to thiopurines can be due to the presence of common genetic polymorphisms affecting the TPMT gene. More recently variations in the number of tandem repeats in the 5' promoter region have been shown to influence TPMT expression in vitro. In this article, we review recent advances in the understanding of the range of inter-individual variation that may be involved in the open reading frame or promoter region of the TPMT gene. We also review the data which have been published regarding the influence such variations may have on both the clinical efficacy and toxicity of the thiopurine drugs.