Reference Interval:
By report
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| 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 UGT1A1 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 detected: (TA)5, (TA)6, (TA)7 and (TA)8.
Clinical Sensitivity/Specificity: The risk of irinotecan toxicity by genotype is shown below (based on data from Br J Cancer (2004) 91:678-82).
TA genotype Diarrhea Neutropenia
6/6 (*1/*1) 17 percent 15 percent
6/7 (*1/*28) 33 percent 27 percent
7/7 (*28/*28) 70 percent 40 percent
Allelic Frequency: *1 (TA)6: Caucasians - 61 percent; Asians - 84 percent; African Americans - 47 percent
*28 (TA)7: Caucasians - 39 percent; Asians - 16 percent; African Americans - 43 percent
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 (TA)5 and (TA)8 alleles on risk of irinotecan toxicities is not well established.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Please refer to Statement C in the Compliance Statements section in the front of the Laboratory Test Directory.
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| CPT Code(s): |
83891 Isolation; 83898 Amplification; 83909 Capillary electrophoresis; 83912 Interpretation and report
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Cross References: |
Irinotecan Toxicity, UGT1A1 |
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