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Dihydropyrimidine Dehydrogenase (DPYD), 3 Variants
2012166
Ordering Recommendation

Predict risk of dose-related toxicity to 5-FU therapy.

Mnemonic
DPYD
Methodology
Polymerase Chain Reaction/Fluorescence Monitoring
Performed
Mon, Thu
Reported
5-10 days
New York DOH Approval Status
This test is New York DOH approved.
Submit With Order
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B). 
Specimen Preparation
Transport 3 mL whole blood. (Min: 1 mL) 
Storage/Transport Temperature
Refrigerated. 
Unacceptable Conditions
Plasma or serum. Heparinized specimens. 
Remarks
 
Stability
Ambient: 72 hours; Refrigerated: 2 weeks; Frozen: 1 month. 
Reference Interval
Interpretive Data
Interpretive Data:
Background information for Dihydropyrimidine Dehydrogenase (DPYD), 3 Variants:
Characteristics:
5-Fluorouracil (5-FU) is the most frequently used chemotherapeutic drug for the treatment of many types of cancer, particularly colorectal adenocarcinoma. Grade III-IV drug toxicity attributed to 5-FU occurs in approximately 16 percent of patients, and may include hematologic, gastrointestinal, and dermatologic complications. In some cases, this toxicity can cause death. When 5-FU is metabolized in the body, approximately 80 percent is catabolized by the dihydropyrimidine dehydrogenase (DPD) enzyme. Variants in the DPYD gene can lead to reduced 5-FU catabolism, resulting in the aforementioned toxicity complications.
Inheritance
: Autosomal codominant.
Cause
: DPYD gene mutations.
DPYD Variants Tested:
Non-functional alleles and toxicity risk:
*13 (rs55886062, c.1679T>G)-Increased risk
*2A (rs3918290, c.1905+1G>A)-Greatly increased risk
c.2846A>T (rs67376798)-Increased risk
A result of negative indicates no variants detected and is predictive of *1 functional alleles and normal enzymatic activity.
Allele Frequency by Population:
*13: Caucasian-0.1 percent; Asian-absent; African American-absent
*2A: Caucasian-0.47-2.2 percent; Asian-absent; African American-absent
c.2846A>T: Caucasians-1.1 percent; Asian-absent; African American-absent
Clinical Sensitivity: Estimated at 31 percent for the DPYD variants analyzed.
Methodology:
Polymerase chain reaction(PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity:
99 percent.
Limitations:
Only the targeted DPYD variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. 5-FU drug metabolism, efficacy and risk for toxicity may be affected by genetic and non-genetic factors that are not evaluated by this test. Genotyping does not replace the need for therapeutic drug monitoring or clinical observation.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
CPT Code(s)
81400; 81479
Components
Component Test Code*Component Chart NameLOINC
2012167DPYD Specimen31208-2
2013096DPYD Genotype
2013097DPYD Phenotype
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • 5FU drug toxicity
  • Capecitabine
  • Dihydropyrimidine
  • DPD
  • DPYD
  • DPYD genotyping
  • Fegafur
  • Uftoral
  • Xeloda