THIOPURIN TOXICITY
(TPMT GENE TEST)
Background
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.
Specimen Shipping
Literature:
Sahasranaman S et al. Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008;64:753-67.
