The metabolism of thiopurine drugs requires the enzyme thiopurine S-methyltransferase (TPMT). Certain haplotypes (combinations of polymorphisms) within the TPMT gene are associated with decreased activity of the enzyme, which can lead to bone marrow toxicity and/or discontinuation of treatment when medication doses are not reduced accordingly. This assay is designed to identify the more common TPMT haplotypes for which there is information available about clinical management.
This report includes haplotypes based on the alleles present for the following polymorphisms: c.719A>G (rs1142345), c.460G>A (rs1800460), c. 238G>C (rs1800462), and c.626-1G>A (rs1800584). Additional sequence variants within the exons that are amplified (4, 6, and 9) are not reported unless they are predicted to result in loss of function (frameshift leading to premature stop codon, nonsense). This test is not designed to detect rare haplotypes.
This test is unable to distinguish between TPMT*3A and TPMT*3D, which are expected to have similar functional effects. It is also unable to distinguish between TPMT*1/*3A and TPMT*3B/*3C. TPMT*3B/*3C is expected to result in reduced enzyme activity; however, it is a rare haplotype combination.