Test Details
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.
Result Turnaround Time
7 - 10 days
Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.
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.
References
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 Instructions
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.
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 |
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.
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
LOINC® Map
| Order Code | Order Code Name | Order Loinc | Result Code | Result Code Name | UofM | Result LOINC |
|---|---|---|---|---|---|---|
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512301 | TPMT Genotype | 71356-0 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512302 | TPMT Metabolic Activity | 79713-4 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512303 | NUDT15 Genotype | 93194-9 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512304 | NUDT15 Metabolic Activity | 93195-6 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512305 | Director Review | 72486-4 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512306 | Interpretation | 56850-1 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 512307 | TPMT and NUDT15 Information | 62364-5 | |
| 512300 | TPMT and NUDT15 Genotyping | 93193-1 | 000000 | MGRM Informed Consent Review | N/A | |
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512301 | |||||
| Result Code Name | TPMT Genotype | |||||
| UofM | ||||||
| Result LOINC | 71356-0 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512302 | |||||
| Result Code Name | TPMT Metabolic Activity | |||||
| UofM | ||||||
| Result LOINC | 79713-4 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512303 | |||||
| Result Code Name | NUDT15 Genotype | |||||
| UofM | ||||||
| Result LOINC | 93194-9 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512304 | |||||
| Result Code Name | NUDT15 Metabolic Activity | |||||
| UofM | ||||||
| Result LOINC | 93195-6 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512305 | |||||
| Result Code Name | Director Review | |||||
| UofM | ||||||
| Result LOINC | 72486-4 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512306 | |||||
| Result Code Name | Interpretation | |||||
| UofM | ||||||
| Result LOINC | 56850-1 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 512307 | |||||
| Result Code Name | TPMT and NUDT15 Information | |||||
| UofM | ||||||
| Result LOINC | 62364-5 | |||||
| Order Code | 512300 | |||||
| Order Code Name | TPMT and NUDT15 Genotyping | |||||
| Order Loinc | 93193-1 | |||||
| Result Code | 000000 | |||||
| Result Code Name | MGRM Informed Consent Review | |||||
| UofM | ||||||
| Result LOINC | N/A |