OMIM: #610460
Locus: 6ü22.3


The thiopurine drugs 6-mercaptopurine (6-MP), azathioprine (AZA) and thioguanine are widely used for the treatment of a variety of diseases, including childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), inflammatory bowel disease, autoimmune hepatitis, rheumatic diseases, dermatologic conditions and in transplantation medicine. However, thiopurine drugs have a relatively narrow therapeutic index and are capable of causing life-threatening toxicity, most often myelosuppression.

Thiopurine S-methyltransferase (TPMT), an enzyme metabolizing these drugs, exhibits a genetic polymorphism. This polymorphism causes leads to reduced TPMT activity in 10% of Caucasians and complete TPMT deficiency in about 1/300 individuals.

In Caucasians, three common TPMT gene variants (*2, *3A, *3C) are associated with diminished TPMT activity. Analysis of TPMT genotypes can help to predict the individual risk for thiopurine toxic side effects.

TPMT genotypes

Class Frequency Genotypes (examples) Commentary
No TPMT Deficiency 89% *1*1 No sign for reduced TPMT activity (wild-type genotype)
Heterozygous deficiency 11% *1*2, *1*3A, *1*3C Reduced TPMT activity
Homozygous deficiency 0,3% *3A*3A, *3A*3C, *3A*2A Deficient TPMT activityt

Indications for testing

  • Estimation of individual risk for thiopurine toxicity.

  • Literatur:
  • Sahasranaman S et al. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008;64:753-67.