TPMT deficiency

The TPMT gene encodes for the enzyme thiopurine S-methyltransferase, which is involved in reactions for breaking down thiopurine drugs. These drugs are used to treat several forms of cancers or disorders involving the immune system, as they suppress the body’s immune system. These drugs are also used to reduce rejection of transplanted organs. The enzyme thiopurine S-methyltransferase performs the S-methylation of aromatic and heterocyclic sulphydryl compounds. This enzyme metabolizes the drugs into inactive compounds. A TPMT deficiency is a reduction in the activity of the TPMT enzyme, which causes a longer presence of the drugs in the body. Consequently, severe side effects from thiopurine therapy can occur, such as suppression of the bone marrow, leading to reduced number of red and white blood cells and platelets. There are multiple nonfunctional TPMT alleles, of which the most common are described underneath.

TPMT*3B

The rs1800460 (460A>G or A154T) is a SNP in the TPMT gene. Risk allele for this SNP is rs1800460(A), which encodes the TPMT*3B allele. This SNP is rare, however more common in Caucasians than African Americans. This SNP can be present together with rs1142345(G), together encoding the TPMT*3A allele.

TPMT*3C

The risk allele for this SNP is rs1142345(G), and when it is the only variant in the TPMT gene, it encodes the TPMT*3C allele. While still rare, it is more common in African-Americans (2.4% of all alleles) than in Caucasians. Note that if the same allele also carries the rs1800460 (A) SNP, the allele is actually a TPMT*3A allele.

TPMT*2

rs1800462, also known as A80P, is a rare SNP in the TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs. The risk allele for this SNP (in orientation to the dbSNP entry) is rs1800462(C), and it encodes the TPMT*2 allele.