UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping
0051332
Ordering Recommendation
May be useful in dosage planning for individuals who will receive high-dose irinotecan, have a history of irinotecan sensitivity, or experience neutropenia while receiving irinotecan. Confirm suspected diagnosis of Gilbert syndrome.
Mnemonic
UGT1A1
Methodology
Polymerase Chain Reaction/Fragment Analysis
Performed
Mon, Thu
Reported
2-7 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
  
Remarks
  
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
By report  
Interpretive Data
Background Information for UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping:
Characteristics:
UGT1A1 is responsible for the clearance of drugs (e.g., irinotecan) and endbiotic compounds (e.g., bilirubin). Irinotecan's major active and toxic metabolite (SN-38) is inactivated by the UGT1A1 enzyme and then eliminated via the bile. UGT1A1 gene mutations cause accumulation of SN-38, which may lead to irinotecan-related toxicities (neutropenia, diarrhea).
Cause:
Variations in TA repeat number in the TATAAA element of the 5' UGT1A1-promoter affects transcription efficiency. The common number of repeats is six [(TA)6, *1 allele], while seven repeats [(TA)7, *28 allele] is associated with reduced transcription activity. Homozygosity for the (TA)7 allele is also associated with Gilbert Syndrome (benign familial hyperbilirubinemia).
Alleles Tested:
*36 allele, (TA)5; *1 allele, (TA)6; *28 allele, (TA)7 and *37 allele, (TA)8.
Clinical Sensitivity/Specificity:
Risk of irinotecan toxicity by genotype (Br J Cancer (2004) 91:678-82).
6/6 (*1/*1): diarrhea 17 percent; neutropenia 15 percent.
6/7 (*1/*28): diarrhea 33 percent; neutropenia 27 percent.
7/7 (*28/*28): diarrhea 70 percent; neutropenia 40 percent.
Allelic Frequency:
*1 (TA)6: Caucasians 0.61, Asians 0.84, African Americans 0.47.
*28 (TA)7: Caucasians 0.39, Asians 0.16, African Americans 0.43.
Methodology:
Polymerase chain reaction followed by size analysis using capillary electrophoresis.
Analytical Sensitivity:
Greater than 99 percent.
Limitations:
Variations in the UGT1A1 gene, other than those targeted, will not be detected. Clinical significance of the rare *36, (TA)5 and *37, (TA)8 alleles in predicting irinotecan toxicities is not well established. Genetic and non-genetic factors other than UGT1A1, may contribute to irinotecan toxicity and efficacy. Diagnostic errors can occur due to rare sequence variations.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.





See Compliance Statement C: www.aruplab.com/CS
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)
81350
Components
Component Test Code*Component Chart Name
0051333UGT1A1 Genotyping Allele 1
0051334UGT1A1 Genotyping Allele 2
0051335UGT1A1 Genotyping Interpretation
2001384UGT1A1 Genotyping Specimen
* 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
  • Irinotecan Toxiicity
  • UGT1A1