TPMT Genotyping

Thiopurine methyltransferase (TPMT) is a phase two drug-metabolizing enzyme expressed in the kidney, red blood cells, liver, and other tissues. TPMT plays a role in the elimination of thiopurine drugs, including mercaptopurine (Purixan®), azathioprine (Imuran®), and thioguanine (Tabloid®).These drugs are typically used to treat acute lymphoblastic leukemia, autoimmune disorders, inflammatory bowel disease and organ transplant rejection. About 10% of the population have intermediate TPMT activity.[64]

Impaired TPMT function can cause life-threatening myelosuppression, a condition in which bone marrow activity is decreased, and other toxicities in patients given normal doses of thiopurines. Impaired function has also been associated with cisplatin-induced ototoxicity in children, although this is not well understood. Individuals with decreased TPMT activity may require thiopurine dosage reductions of 50 to 90 percent to tolerate therapy and reduce the risk of adverse reactions.[71] Genetic alleles tested for TPMT are *2,*3A-C,*4.

Indications for TPMT Testing

Patients who are initiating thiopurine medications or who are experiencing adverse effects or low efficacy may be good candidates for TPMT testing. Testing may confirm the presence of genotypes that affect the metabolism of drugs that are metabolized by this pathway. Assessment of medical necessity for testing is up to the provider’s clinical judgment.