Pharmacogenetics of thiopurine therapy: from thiopurine S-methyltransferase to S-adenosylmethionine

Background The efficiency and safety of the thiopurine therapy rely on the concentration of patient's cytotoxic thioguanine nucleotides (TGN), which in turn depend on the deactivation of thiopurine drugs by thiopurine S-methyltransferase (TPMT). The activity of TPMT largely depends on the presence of genetic polymorphisms. Determination of mutations in the TPMT gene before starting 6-mercaptopurine (6-MP) therapy represents a quick, simple and costeffective strategy to individualize thiopurine dosing. However, TPMT phenotype-to-genotype correlation is not complete, indicating a need for identification of novel biomarkers. The prime candidate is S-adenosylmethionine (SAM) which by binding into the active site of TPMT stabilizes its structure and consequently influences the metabolism and toxicity of thiopurine drugs [1].