TPMT encodes a gene best known for helping to break down potentially toxic products of the antineoplastic agents 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressant azathioprine (AZA). Individuals homozygous for two nonfunctional TPMT variants are at high risk for toxic side effects if in the course of their treatment they are treated with such drugs.
The most common nonfunctional TPMT alleles, as defined by certain SNPs, are:
- rs1800460, known as 460A>G or A154T, potentially encoding the TPMT*3A allele;
- rs1142345, known as 719A>G or Y240C, potentially encoding the TPMT*3C allele;
- rs1800462, known as A80P, encoding the TPMT*2 allele
- rs56161402, known as R215H, encoding the TPMT*8 allele
- rs1800584, encoding the TPMT*4A allele
Although these alleles are all relatively rare, they do vary in frequency between ethnic populations; for example, the most common TPMT variant in African-Americans is Y240C (2-3% of all alleles; but 50% of all variants), whereas the most common variant in Caucasians is A154T (5% of all alleles).
More complete details on effects of variations of this gene on drug metabolism are provided PharmGKB.