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Thiopurine Methyltransferase (TPMT) Genotyping, 4 Variants
2012233
Ordering Recommendation

Genotype test to assess risk, due to genetics, for severe myelosuppression with standard dosing of thiopurine drugs. Use for individuals being considered for thiopurine therapy or who have had an adverse reaction to thiopurine therapy. Preferred test for patients with recent heterologous blood transfusion. Can be performed irrespective of thiopurine therapy.

Mnemonic
TPMT DNA
Methodology
Polymerase Chain Reaction/Fluorescence Monitoring
Performed
Mon, Thu
Reported
5-10 days
New York DOH Approval Status
This test is New York DOH approved.
Submit With Order
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B). 
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL) 
Storage/Transport Temperature
Refrigerated. 
Unacceptable Conditions
Plasma or serum. Heparinized specimens. 
Remarks
 
Stability
Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month. 
Reference Interval
By report
Interpretive Data
Background Information for Thiopurine Methyltransferase (TPMT) Genotyping, 4 Variants:
Characteristics:
Thiopurine therapy is used in the treatment of autoimmune diseases, inflammatory bowel disease and acute lymphoblastic leukemia and is also used to prevent rejection after solid organ transplant. Thiopurine drugs (eg, Azathioprine, 6-mercaptopurine, 6-thioguanine) are antimetabolites and must be metabolized to 6-thioguanine nucleotides (6-TGN) for activity. The inactivation of thiopurine drugs is primarily catalyzed by TPMT. Variants in the TPMT gene can lead to low TPMT enzyme activity, resulting in accumulation of cytotoxic metabolites and increased risk for drug-related myelotoxicity with standard doses of thiopurine drugs.
Incidence of TPMT deficiency: In the general population,approximately 0.3 percent of individuals have low TPMT activity and 10 percent have intermediate TPMT activity.
Allele Frequencies:
TPMT *2: African 0.000792, Asian 0.0, Caucasian 0.00190, Mediterranean 0.00408, Mexican 0.00592, Middle Eastern 0.00749
TPMT *3A: African 0.00198, Asian 0.0001118, Caucasian 0.0356, Mediterranean 0.0254, Mexican 0.0533, Middle Eastern 0.0114
TPMT *3B: African 0.0, Asian 0.0, Caucasian 0.000461, Mediterranean 0.00426, Mexican 0.00690, Middle Eastern 0.00562
TPMT *3C: African 0.0495, Asian 0.0157, Caucasian 0.004205, Mediterranean 0.00545, Mexican 0.00888, Middle Eastern 0.00562
Inheritance: Autosomal co-dominant.
Cause: TPMT gene variants resulting in enzyme deficiency.
Variants Tested:
TPMT deficiency alleles: *2 (c.238G>C; p.Ala80Pro), *3A (c.[460G>A;719A>G]; p.[Ala154Thr;Tyr240Cys]), *3B (c.460G>A; p.Ala154Thr), *3C (c.719A>G; p.Tyr240Cys).
No variants detected is predictive of *1 functional alleles and normal TPMT enzyme activity.
(Variants are numbered according to NM_000367 transcript)
Clinical Sensitivity: 95 percent.
Methodology: Polymerase chain reaction(PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Only the targeted TPMT variants will be detected by this panel. Because the complex *3A allele contains the variants found in the *3B and *3C alleles, this test cannot distinguish the 3A/Negative genotype (intermediate enzyme activity) from the rare *3B/*3C genotype (no or low enzyme activity). This test does not assess for TPMT variants associated with ultra-high enzyme activity. Genotyping will reflect donor status in patients who have received allogenic stem cell or bone marrow transplants. TPMT enzyme activity, drug metabolism and risk for adverse reactions to thiopurines may be affected by additional genetic and non-genetic factors not evaluated by this test. Diagnostic errors can occur due to rare sequence variations. Genotyping does not replace the need for therapeutic drug monitoring and clinical observation.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Components
Component Test Code*Component Chart NameLOINC
2012238TPMT Genotype Specimen31208-2
2012239TPMT Genotype41048-0
2012240TPMT Predicted Phenotype36922-3
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • 6-mercaptopurine
  • 6-MP
  • 6-TG
  • 6-thioguanine
  • AZA toxicity
  • Azathioprine
  • S-adenosyl-L-methionine genotype
  • Thioguanine
  • Thiopurine
  • Thiopurine S-methyltransferase genotype
  • TPMT genetics
  • TPMT mutation