Test Directory

• TPMT Genotype
• TPMT Metabolic Activity
• NUDT15 Genotype
• NUDT15 Metabolic Activity

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.

Specimen Type: Whole Blood

Alternate Specimen Type: Buccal Swab

Collection Container: Lavender Top (EDTA)

Alternate Collection Container: Pale Yellow Top (ACD, Solution A or B) or Buccal Swab Kit

Desired Specimen Volume: 2 mL

Alternate Specimen Volume: 4 swabs

Whole Blood:

1. Collect a lavender top (EDTA) tube via venipuncture.

Buccal Swab:

1. Collect 4 buccal swabs.

Whole Blood:

1. Transport 2 mL of whole blood in the original collection container.

Buccal Swab:

1. Transport buccal swab kit (4 swabs) at room temperature.

Transport whole blood to the laboratory refrigerated. 

Transport Buccal swabs to the laboratory at room temperature.

• Quantity not sufficient for analysis
• Improper container
• Single buccal swab
• Wet buccal swab
• Buccal swabs without outer collection envelope
• Severely damaged buccal swab envelope
• Buccal swab envelope received open
• Frozen glass tube

See patient report.

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.

• Nudix Hydrolase 15
• Thiopurine Methyltransferase
• TPMT and NUDT15 Genotyping