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HelpTest ID UGTIO UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene Sequencing, Irinotecan Hypersensitivity, Saliva
Useful For
Identifying individuals who are at increased risk of adverse drug reactions with drugs that are metabolized by UGT1A1, including irinotecan, atazanavir, nilotinib, pazopanib, and belinostat.
Genotyping patients who prefer not to have venipuncture done
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| UGT1O | UGT1A1 Gene Sequence, Irinotecan | No | Yes |
| UGTSQ | UGT, Full Gene Sequencing | No | Yes |
Testing Algorithm
See UGT1A1 Test-Ordering Algorithm in Special Instructions
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) Followed by Gene Sequencing
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name
UGT1A1 Sequence, Irinotecan, SalivaSpecimen Type
SalivaMultiple saliva genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Oragene DNA Self-Collection Kit (T651: fees apply)
Specimen Volume: Full tube
Collection Instructions:
1. Fill tube to line.
2. Send specimen in original container per kit instructions.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Saliva | Ambient | |
Clinical Information
Following primary metabolism by the phase I enzymes (by oxidation, reduction, dealkylation, and cleavage in the intestines and liver), many drugs and their metabolites are further modified for excretion by a group of conjugative, phase II enzymes. One of these phase II enzymes, uridine diphosphate (UDP)-glycuronosyl transferase 1A1 (UGT1A1), is responsible for bilirubin conjugation with glucuronic acid. This renders the bilirubin water soluble and permits excretion of the bilirubin-glucuronide conjugates in urine.(1)
UGT1A1 is involved in the metabolism of irinotecan, a topoisomerase I inhibitor. Irinotecan is a chemotherapy drug used to treat solid tumors including colon, rectal, and lung cancers. It is a prodrug that forms an active metabolite, SN-38. SN-38 is normally inactivated by conjugation with glucuronic acid followed by biliary excretion into the gastrointestinal tract. If UGT1A1 activity is impaired or deficient due to mutations in the coding region or promoter TA (thymine, adenine) repeat polymorphisms, SN-38 fails to become conjugated with glucuronic acid, increasing the concentration of SN-38. This can result in severe neutropenia. The combination of neutropenia with diarrhea can be life-threatening.(2,3)
Additional drugs have also been associated with an increased risk for adverse outcomes if the patient has reduced UGT1A1 enzyme activity. The FDA drug labels for nilotinib, pazopanib, and belinostat all contain warnings for an increased risk (incidence) of adverse outcomes in patients who have UGT1A1 alleles associated with reduced activity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) released guidelines for atazanavir treatment, indicating that patients with homozygous UGT1A1 alleles associated with reduced activity or decreased expression should consider an alternate medication due to a significant risk for developing hyperbilirubinemia (jaundice).
The UGT1A1 gene maps to chromosome 2q37 and contains 5 exons. The promoter, exons, exon-intron boundaries, and a region in the distal promoter called the "phenobarbital response enhancer module," which is associated with transcriptional activity of the gene, are assessed for variants in this assay.(4)
Reference Values
An interpretive report will be provided.
Cautions
Samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient’s genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic blood or marrow transplantation, a pretransplant DNA specimen is recommended for testing.
UGT1A1 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's UGT1A1 status.
An alternative splice site for exon 5 (referred to as exon 5b) has been discovered and described in the literature. This new exon is described to have a decrease in enzymatic activity (compared to exon 5a [previously known as exon 5]), but little is known about the frequency of exon 5b or how it impacts irinotecan therapy. Currently, we are not testing or sequencing exon 5b. We will continue to monitor the literature for new information on exon 5b.
Rare variants exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Day(s) Performed
Tuesday; Varies
Report Available
7 daysPerforming Laboratory
Mayo Medical Laboratories in Rochester
Test Classification
See Individual Test IDsCPT Code Information
81350-UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide AI) (eg, irinotecan metabolism), gene analysis, common variants (eg, *28, *36, *37)