This PCR-based allele discrimination assay is performed on genomic DNA and detects the four most common abnormal alleles of the thiopurine methyltransferase (TPMT) gene, which are TPMT*2 (238G>C), TPMT*3A (460G>A + 719A>G), TPMT*3B (460G>A), and TPMT*3C (719A>G). The status of the abnormal alleles tested is reported as not detected, heterozygous, or homozygous. The TPMT enzyme activity associated with the genotype is reported as normal, intermediate, or low or no activity. The abnormal alleles tested in this assay account for >95% cases of low or undetectable TPMT enzyme activity.
Thiopurine drugs are used to treat patients with hematologic cancers, autoimmune disease, and post-transplant organ rejection. Patients with inherited deficiencies in TPMT who are treated with full doses of thiopurines are subject to toxicity with effects including acute myelosuppression, liver toxicity, pancreatitis, and flu-like symptoms. Testing for TPMT status before initiating thiopurine therapy is recommended so initial doses can be adjusted. Approximately 10-15% of individuals are heterozygous for a mutant allele and have intermediate enzyme activity. Approximately 0.3% have two mutant alleles and have low or undetectable enzyme activity.
Peripheral blood: 5 mL in EDTA tube
Use cold pack for transport, making sure cold pack is not in direct contact with specimen.