The Test Sample
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 include suppression of the bone marrow (myelosuppression) and/or very reduced levels of blood cells (hematopoetic toxicity). 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 production is tested 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 wild-type gene and one gene variation associated with decreased TPMT (heterozygous) and intermediate 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 quantify 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. For more on this, see Common Questions #1.
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.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
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.