Thiopurine methyltransferase (TPMT)
- Also Known As:
- TPMT RBC
- TPMT Genotype
- TPMT Phenotype
- Formal Name:
- Thiopurine S-methyltransferase Phenotype
- Thiopurine S-methyltransferase Genotype

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.At a Glance
Why Get Tested?
To detect a thiopurine methyltransferase (TPMT) deficiency and determine your risk of developing severe side effects if treated with the class of immune-suppressing thiopurine drugs that includes azathioprine, mercaptopurine, and thioguanine
When To Get Tested?
Typically, prior to thiopurine drug treatment; this is a specialized test and is not routinely ordered.
Sample Required?
A blood sample drawn from a vein in your arm or a swab from inside your cheek (i.e., buccal swab)
Test Preparation Needed?
For measuring TPMT enzyme activity (TPMT phenotyping), the test must be performed prior to taking a thiopurine drug since it may affect results; for the genetic test (TPMT genotyping), no specific test preparation is needed.
What is being tested?
Thiopurine methyltransferase (TPMT) is an enzyme that breaks down (metabolizes) a class of drugs called thiopurines. These drugs are used to suppress the immune system and are prescribed to treat various immune-related conditions or blood disorders (e.g., leukemia). The activity level of the TPMT enzyme, or the genetics underlying the enzyme’s activity, is tested before thiopurine drug therapy to make sure that individuals treated with the drugs can metabolize them.
Examples of thiopurines include azathioprine, mercaptopurine, and thioguanine. These medications are used to treat diseases such as acute lymphoblastic leukemia, inflammatory bowel disease, and autoimmune disorders. They may also be prescribed for organ transplant recipients to help delay or prevent organ rejection. If someone’s TPMT activity is too low, the person may not effectively metabolize thiopurines, which can lead to severe side effects.
About one person in every 300 is severely deficient in TPMT, and about 10% of the population in the U.S. has lower than normal levels of TPMT. Individuals in both categories are at an increased risk for thiopurine drug toxicity, which can affect the activity of the bone marrow (myelosuppression) and lead to very reduced levels of blood cells, such as red blood cells, white blood cells and platelets (hematopoetic toxicity). This can lead to complications such as anemia, serious infections, and/or excessive bleeding.
These side effects can cause an individual to become severely ill and may even be life-threatening. These side effects can be avoided if TPMT testing is done before starting thiopurine treatment.
There are two ways to determine whether an individual is at risk of side effects from thiopurine therapy:
- TPMT activity test (phenotype)—this method tests the activity level of the enzyme thiopurine S-methyltransferase (TPMT) in a person’s red blood cells. Depending on the enzyme activity level, a person may be prescribed a standard dose of the thiopurine drug, a reduced dose of the thiopurine drug, or a different drug other than a thiopurine.
- TPMT genetic test (genotype)—an alternative test to TPMT enzyme activity level is a genetic test that can identify genetic variations in the TPMT gene. This genetic test identifies individual genetic differences associated with risk for thiopurine toxicity. Each person has two copies of the TPMT gene. Most people have two copies of “wild type” TPMT that produce sufficient TPMT enzyme. Approximately 10% of people have one copy of the wild-type gene and one copy of a gene variation associated with decreased TPMT (heterozygous) and intermediate enzyme activity. Approximately one in 300 individuals have two copies of TPMT with variations resulting in little or no enzyme activity (homozygous). While numerous variations can occur in TPMT, there are five variations in particular that have been proven to be associated with TPMT deficiencies. Most genetic tests look for these five variations, although depending on the method used, more variations can be detected.This genetic test provides information about a person’s likely response to thiopurines, but it will not measure how much TPMT enzyme is actually being made by the body. There can be significant person-to-person and ethnic variability in TPMT production, even in people with the same gene variations.
A third, different kind of test may be used after thiopurine treatment begins. A test that measures thiopurine breakdown products (thiopurine metabolites) may be used to monitor therapy and adjust doses.
How is the sample collected for testing?
For both genetic and enzyme activity testing, a blood sample is taken by needle from a vein in the arm. Alternatively, for the genetic test alone, a swab of cells from the inside cheek (buccal swab) may be collected.
Is any test preparation needed to ensure the quality of the sample?
For the method that measures TPMT enzyme activity, taking a thiopurine drug could lead to falsely low results, so the test should be performed prior to starting therapy. For the genetic test (TPMT genotyping), no specific test preparation is needed.
Common Questions
View Sources
Sources Used in Current Review
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Sources Used in Previous Reviews
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