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.
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.
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.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Linnea Baudhuin, Phd, DABMG. Assistant Professor of Laboratory Medicine. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Nguyen et al. (May 15, 2011). Thiopurine methyltransferase (TPMT) genotyping to predict myelosuppression risk. PLoS Currents. Evidence on Genomic Tests. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094768/ through http://www.ncbi.nlm.nih.gov. Accessed March 2013.
(2013). Thiopurine Methyltransferase, Red Blood Cell. ARUP Laboratories. Available online at http://www.aruplab.com/guides/ug/tests/0092066.jsp through http://www.aruplab.com. Accessed March 2013.
(Updated Oct. 2011). TPMT Genotype. Quest Diagnostics.Available online at http://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_TPMT_Genotype through http://www.questdiagnostics.com/. Accessed March 2013.
Azathioprine Metabolism and TPMT. Medscape. Availabe online at http://emedicine.medscape.com/article/1829596-overview through http://emedicine.medscape.com. Accessed March 2013.
(2003) Relling, M. Genetics and Anti-Leukemia Therapy: The TPMT Story. American Childhood Cancer Organization. Available online at http://www.acco.org/Information/tpmt.aspx through http://www.acco.org. Accessed April 2013.
Bruns D, Ashwood E, Burtis C, eds (2007). Fundamentals of Molecular Diagnostics, Saunders Elsevier, St. Lous, Missouri, Pp 200-203.
Sources Used in Previous Reviews
Dr. Jonathon Berg. City Hospital, Birmingham, England.
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp. 479.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp. 1420.
(2008 July). Thiopurine Methyltransferase, Red Blood Cell. ARUP Laboratories Technical Bulletin [On-line information]. PDF available for download at http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/Thiopurine%20Methyltransferase,%20Red%20Blood%20Cell.pdf through http://www.aruplab.com. Accessed on 1/4/09.
Ansari, A.et. al (2008 December 17). Prospective Evaluation of the Pharmacogenetics of Azathioprine in the Treatment of Inflammatory Bowel Disease [On-line information]. Available online at http://www.medscape.com/viewarticle/584257 through http://www.medscape.com. Accessed on 1/4/09.
Aberra, F. and Lichtenstein, G. (Review Article: Monitoring of Immunomodulators in Inflammatory Bowel Disease. Medscape from Aliment Pharmacol Ther. 2005; 21 (4): 307-319. [On-line information]. Available online at http://www.medscape.com/viewarticle/499922_1 through http://www.medscape.com. Accessed on 1/4/09.
Derijks, L. et. al. (2006 September 26). Thiopurines in Inflammatory Bowel Disease. [On-line information]. Available online at http://www.medscape.com/viewarticle/543562 through http://www.medscape.com. Accessed on 1/4/09.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER and Bruns DE, eds. 4th ed. St. Louis, Missouri: Elsevier Saunders; 2006, Pg 1273.