NUDT15 / TPMT and thiopurines

The enzymes NUDT15 and TPMT are involved in the metabolisation of, amongst other things, the anti-tumour drugs mercaptopurine and thioguanine, as well as immunosuppressive drugs like azathioprine. These drugs are used in the treatment of cancer and Crohn’s disease, in the event of organ transplants and to treat inflammatory diseases such as rheumatoid arthritis and inflammation of the bowel, liver or skin, for example. If you have increased sensitivity to thiopurines, there is a higher risk of side effects. Such increased sensitivity may be partly explained by genetic variations in the NUDT15 gene and TPMT gene.

Azathioprine and the enzyme NUDT15 and TPMT

Azathioprine is processed to a large extent by the enzyme NUDT15 and TPMT. The activity of this enzyme can vary considerably depending on your genetic predisposition, which means the efficacy of azathioprine can also differ from person to person.

Information about your genetic predisposition may therefore provide grounds for extra vigilance in relation to a treatment with azathioprine.

Read more about Azathioprine »

Mercaptopurine and the enzyme NUDT15 and TPMT

Mercaptopurine is processed to a large extent by the enzyme NUDT15 and TPMT. The activity of this enzyme can vary considerably depending on your genetic predisposition, which means the efficacy of mercaptopurine can also differ from person to person.

Information about your genetic predisposition may therefore provide grounds for extra vigilance in relation to a treatment with mercaptopurine.

Read more about Mercaptopurine »

Thioguanine and the enzymes NUDT15 and TPMT

Thioguanine is processed to a large extent by the enzymes NUDT15 and TPMT. The activity of these enzymes can vary considerably depending on your genetic predisposition, which means the efficacy of thioguanine can also differ from person to person.

Information about your genetic predisposition may therefore provide grounds for extra vigilance in relation to a treatment with thioguanine.

Read more about Tioguanine »

Genetic predisposition
Efficacy and your individual risk of side effects in the event of treatment with thiopurines such as azathioprine, mercaptopurine and thioguanine may be partly explained by genetic variations. For example, it is known that mutations in the NUDT15 gene and TPMT gene can reduce enzyme activity. As drugs from the thiopurine group need to be dosed precisely, it may be important to know what genotype you have. People with certain mutations in the enzyme NUDT15 and/or TPMT have reduced enzyme activity and may therefore be extra sensitive to thiopurines.
Reduced activity of the enzyme NUDT15 is common in Asians, but relatively rare in Europeans. Genotyping of the TPMT enzyme reveals an abnormality in around 10% of the European population and in 2-5% of Asians.
When a genotype is determined variations are indicated by two so-called alleles. Each allele has a name consisting of an asterisk and a number.
At iGene we determine the following variants (alleles) of the NUDT15 and TPMT genes: NUDT15*3, NUDT15*4, NUDT15*5, TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*4, TPMT*11, TPMT*14, TPMT*15, TPMT*23, TPMT*29 and other (classified as *1).

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