ARUP's Laboratory Test Directory

UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping : 0051332
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Additional Technical Information
  


Mnemonic: UGT1A1

Ordering Recommendation: May be useful in dose planning for individuals who will receive high-dose irinotecan, who have a history of irinotecan sensitivity, or who experience neutropenia while receiving irinotecan.
Methodology: Polymerase Chain Reaction/Fragment Analysis
Performed: Mon, Thu
Reported: 2-7 days
Specimen Required: 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.

Stability (collection to initiation of testing): 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's 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.



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
CPT Code(s): 81350
Cross References: Irinotecan Toxiicity (UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping), UGT1A1 (UDP Glucuronosyltransferase 1A1 (UGT1A1) Genotyping)