TPMT and NUDT15 Genotyping

Also known as: Nudix Hydrolase 15, Thiopurine Methyltransferase

Clinical Use

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.

Special Instructions

Not provided.

Limitations

This test cannot distinguish between NUDT15 *2 and *3 alleles, reporting them as *2 or *3, and cannot differentiate between TPMT *1/*3A and rare *3B/*3C genotypes. It does not detect all possible variant alleles in TPMT and NUDT15. Consider environmental, dietary, and additional medications when interpreting results, as these factors may influence drug metabolism. Genetic results should be reviewed alongside clinical data for comprehensive analysis.

Test Details