Specimen Requirements

Stability

Days Performed

2 days per week

Turnaround Time

5 days

Methodology

Reference Range

Clinical Info

TPMT genotyping test is used for identifying patients at risk for myelosuppression with the standard dosage of thiopurine drugs, and for adjusting the drug dosage or to select alternate drug therapy. Reference Range for the test is TPMT*1/TPMT*1. No variants detected is an indication of homozygous wild type (two *1 functional alleles), which is associated with normal TPMT enzyme activity. Patients with two functional *1 alleles are predicted to have normal (high or extensive) TPMT enzyme activity. Patients with one functional allele (*1) and one nonfunctional allele (*2, *3A, *3B, or *3C) are predicted to have intermediate TPMT enzyme activity. These patients are at risk for severe myelosuppression or drug toxicity, and may require only a lower than standard dosage of thiopurine drugs. Patients with two nonfunctional allele (*2, *3A, *3B, or *3C) are predicted to have deficient (no or low) TPMT enzyme activity. These patients are at a greater risk (almost 100%) of experiencing myelosuppression, who may require even a reduced dosage of thiopurine drugs than patients with one nonfunctional allele and should be considered for an alternate drug therapy.

Clinical Limitation

The TPMT genotyping assay detects only TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C variants. This assay does not interrogate other TPMT variants and therefore their genotype-phenotype associations to thiopurine drugs are not indicated. This genotyping test will not distinguish *1/*3A heterozygous from the rare *3B/*3C genotype, which can only be identified with a test for TPMT enzyme activity.

Clinical Reference

Relling MV et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing. Clin Pharmacol Ther. 2013 update. 93:324-325.