UGT1A1 Gene Analysis Common Variants
Label Mnemonic: UGT1A1
Epic Lab Code: LAB4221
Downtime Form: A-1a Miscellaneous Request
Commercial Mail-out Laboratory
5231 RCP
356-8593
Specimen(s):
Whole blood
Collection Medium:
Lavender top tube 3 mL (EDTA)
Alternate Collection Media:
Pink top tube 6 mL (K2-EDTA) or Yellow top tube 8.5 mL (ACD solution A)
Minimum:
Preferred Minimum: 3 mL whole blood from lavender top(EDTA) tube
Absolute Minimum: 1 mL whole blood from lavender top(EDTA) tube
Rejection Criteria:
Frozen specimens
Turn Around Time:
2-7 days upon receipt at reference laboratory
Reference Range:
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 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: *36 allele, (TA)5; *1 allele, (TA)6; *28 allele, (TA) 7 and *37 allele, (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% 15% 6/7 (*1/*28) 33% 27% 7/7 (*28/*28) 70% 40% Allelic Frequency: *1 (TA)6: Caucasians - 61%; Asians - 84%; African Americans - 47% *28 (TA)7: Caucasians - 39%; Asians - 16%; African Americans - 43% Analytical Sensitivity: Greater than 99 percent
Test 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.
Methodology:
Polymerase Chain Reaction/Fragment Analysis
CPT Code:
81350