TPMT and NUDT15 Genotyping

CPT: 81306; 81335
Updated on 09/8/2024
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Synonyms

  • Nudix Hydrolase 15
  • Thiopurine Methyltransferase

Expected Turnaround Time

7 - 10 days

7 - 10 days



Specimen Requirements


Specimen

Whole blood or Labcorp buccal swab kit (buccal swab collection kit contains 4 swabs and instructions for use of a buccal swab)


Volume

2 mL whole blood or one buccal swab kit (4 swabs)


Minimum Volume

1 mL whole blood or two buccal swabs


Container

Lavender-top (EDTA) tube or yellow-top (ACD) tube or Labcorp buccal swab kit


Collection

Collect specimen in a lavender-top (EDTA) or yellow-top (ACD) tube, or use a buccal swab kit (4 swabs). Ship whole blood specimen at room temperature or frozen. Ship buccal swab kit at room temperature.


Storage Instructions

Maintain whole blood specimen at room temperature or refrigerated for 28 days, frozen for 2 years. Maintain buccal swabs at room temperature for 2 months.


Stability Requirements

Temperature

Period

Room temperature

Whole Blood: 28 days

Swabs: 2 Months

Refrigerated

Whole Blood: 28 days

Swabs: Unstable

Frozen

Whole Blood: 2 years

Swabs: Unstable


Causes for Rejection

Quantity not sufficient for analysis; improper container; single buccal swab; wet buccal swab; buccal swabs without collection envelope; buccal swab envelope received open; frozen glass tube

Hemolysis; quantity not sufficient for analysis; improper container; single buccal swab; wet buccal swab; buccal swabs without collection envelope; buccal swab envelope received open; frozen glass tube

Quantity not sufficient for analysis; improper container; single buccal swab; wet buccal swab; buccal swabs without collection envelope; buccal swab envelope received open; frozen glass tube


Test Details


Use

The thiopurine methyltransferae (TPMT) and nudix hydrolase 15 (NUDT15) genes encode drug-metabolizing enzymes involved in the metabolism of several clinically important drugs, including the immunosuppressant's azathioprine, mercaptopurine and thioguanine. The TPMT and NUDT15 enzymes have similar functions in a shared thiopurine-metabolizing pathway; genotype and metabolic activity for TPMT and NUDT15 may therefore be considered together when assessing possible effects on drug response. Individuals with some variant TPMT and NUDT15 alleles may experience a reduced therapeutic response and may be at risk for side effects from drugs that are metabolized by TPMT and NUDT15. TPMT and NUDT15 genotype information can be utilized to predict TPMT and NUDT15 metabolic activity, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by TPMT and NUDT15. For example, thiopurine use in an individual with poor or intermediate TPMT and/or NUDT15 metabolism is associated with an accumulation of cytotoxic metabolites and an increased risk for myelosuppression. In these instances, alternative doses or drugs may be considered.

Variation in the TPMT and NUDT15 genes can result in normal (NM), intermediate (IM), possible intermediate (Poss IM), poor (PM) and indeterminate (IND) drug-metabolizing phenotypes. In general, relative to the *1 allele (normal function), TPMT *2, *3A, *3B, *3C and NUDT15 *2 and *3 alleles have no function, while the NUDT15*4 allele has an uncertain function.


Limitations

This assay cannot distinguish between NUDT15 *2 and *3 alleles, genotype reported as *2 or *3; this distinction is not thought to be clinically relevant because both have no function. This assay is also unable to distinguish between the more likely TPMT *1/*3A genotype (intermediate TPMT activity) and the very rare TMPT *3B/*3C genotype (poor TMPT activity, genotype reported as *1/*3A or unlikely *3B/*3C, metabolic activity reported as likely intermediate; these possibilities can be distinguished by testing TPMT enzyme levels (use Test no. 510750).

The exact effect of a particular genotype on individual drugs can vary. In addition to genotype, the metabolism of drugs may be influenced by additional factors that include environmental, dietary and other medications; these factors and others should be considered prior to initiating a new therapy. All results must be interpreted in the context of other test results and clinical findings. Results do not rule out the possibility of other variant alleles in TPMT and NUDT15 or other variant alleles in other drug metabolism pathways. Patients should speak with their health care provider about the individual results of this test.

Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

DNA analysis is performed by allele-specific real-time polymerase chain reactions (RT-PCR) to detect single-nucleotide polymorphisms (SNPs) within the TPMT and NUDT15 genes and to assign variant TPMT *2, *3A, *3B and *3C and NUDT15 *2, or *3 and *4 alleles, *1 denotes detection of the reference (wild-type) sequence at the assessed alleles. No other variants in this gene are detected by this assay.


References

Dean L. Thiogaunine therapy and TPMT and NUDT15 genotype. Pratt VM, Scott SA, Pirohamed M, Esquivel B, kattman BL, Malheiro AJ, eds. In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012.2012 Sep 20 [updated 2020 Aug 7].28520351
Pratt VM, Cavallari LH, Fulmer ML, et al. TPMT and NUDT15 genotyping recommendations: a joint consensus recommendation of the Association for Molecular Pathology, Clinical Pharmcogenetics Implementation Consortium, College of American Pathologists, Dutch Pharmacogenetics Working Group of Dutch Phamacists Association, European Society for Pharmacogenomics and Personalized Therapy, and Pharmacogenomics Knowledgebase. J Mol Diagn. 2022 Oct;24(10):1051-1063.35931343
Relline MV, Schwab M, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clin Pharmacol Ther. 2019 May;105(5):1095-1105.30447069
US Food and Drug Adminstration (FDA). Table of Pharmacogenetic Associations. FDA website: https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations. Accessed April 2023.

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