DPYD Genotyping

The dihydropyrimidine dehydrogenase gene (DPYD) produces a drug-metabolizing enzyme, dihydropyrimidine dehydrogenase (DPD), which is involved in the metabolism of several clinically important drugs including the fluoropyrimidines 5-fluorouracil and capecitabine, which are frequently used as chemotherapeutic drugs. Individuals with some variant DPYD alleles are at increased risk for side effects from drugs that are metabolized by DPD. DPYD genotype information can be utilized to predict DPD metabolic activity, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by DPD. For example, DPD eliminates over 80% of the drug 5-fluoracil. An intermediate or poor metabolizer may be subjected to a buildup of 5-fluoracil, which can be associated with severe toxicity. Substantial evidence supports the use of DPYD genotyping for guiding fluoropyrimidine dosage/use.

Variation in the DPYD gene can result in normal (NM), intermediate (IM) and poor (PM) drug-metabolizing genotypes. In general, relative to the reference sequence (normal function), c.2846A>T (rs67376798), c.1236G>A (in HapB3 with c. 1129-5923C>G, rs56038477) and c.557A>G (rs115232898), variants have decreased function while c.1905+1G>A (previously *2A, rs3918290) and c.1679T>G (previously *13, rs55886062) variants have no function.

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 initialing 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 DPYD 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.

DNA analysis is performed by allele-specific real-time polymerase chain reactions (RT-PCR) to detect single-nucleotide polymorphisms (SNPs) within the DPYD gene and to assign variant DPYDc.1905+1G>A (previously *2A, rs3918290), c.1679T>G (previously *13, rs55886062), c.2846A>T (rs67376798), c.1236G>A (in HapB3 with c.1129-5923C>G, rs56038477), and c.557A>G (rs115232898) alleles. Reference denotes detection of the wild-type sequence at the assessed positions. No other variants in this gene are detected by this assay.