TPMT and NUDT15

Background Information for TPMT and NUDT15:
Characteristics: Thiopurine drug therapy is used for autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent rejection after solid organ transplant. The inactivation of thiopurine drugs is catalyzed in part by thiopurine methyltrasferase (TPMT) and nudix hydrolase 15 (NUDT15). Variants in the TPMT and/or NUDT15 genes are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. These effects on thiopurine catabolism can be additive.
Inheritance: Autosomal codominant.
Cause: TPMT and NUDT15 variants affect enzyme expression or activity.
Variants Tested: See the Additional Technical Information document.
Clinical Sensitivity: 95 percent.
Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Only the targeted TPMT and NUDT15 variants will be detected by this test. Because the complex TPMT*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). Genotyping may reflect donor status in patients who have received allogenic stem cell or bone marrow transplants within 2 weeks of specimen collection. Actual enzyme activity and expression 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. 

Please note the information contained in this report does not contain medication recommendations, and should not be interpreted as recommending any specific medications. Any dosage adjustments or other changes to medications should be evaluated in consultation with a medical provider. 

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.