Test ID: U1A1
UDP-Glucuronosyl Transferase 1A1 TA Repeat Genotype, UGT1A1
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Identifying individuals who are at increased risk of adverse drug reactions with irinotecan and who should be considered for decreased dosing of the drug.
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See UGT1A1 Test-Ordering Algorithm in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Method Name A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) with Fragment Analysis by Capillary Gel Electrophoresis
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Irinotecan glucuronidation
Irinotecan metabolism
Phenol/Bilirubin UDP-Glucuronosyltransferase
UDP-Glucosyltransferase 1
UGT1A1
Uracil Glucuronyl transferase
Uridine Diphosphate Glucosyltransferase 1
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple whole blood EDTA genotype tests can be performed on a single specimen after a single extraction. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA) or lavender top (EDTA) microtube
Specimen Volume: 3 mL
Collection Instructions:
1. Send specimen in original tube.
2. If submitting specimen in microtube, place inside a larger tube or vial for transport.
Additional Information:
1. Bone marrow and liver transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
2. Transfusions will interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
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 (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood EDTA | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
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, 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.
The most common cause of irinotecan-induced neutropenia results from insertion of extra TA (thymine, adenine) repeats in the TATA box of the UGT1A1 promoter. This results in decreased expression of the UGT1A1 gene in individuals homozygous for these promoter polymorphisms. The number of TA repeats is inversely related to gene expression. Individuals with normal levels of UGT1A1 expression have 6 copies of the TA repeat in the promoter (referred to as the *1 allele) or more rarely 5 copies of the TA repeat (referred to as *36). Individuals with decreased expression of UGT1A1 have 7 TA repeats (*28 allele) or 8 TA repeats (*37). Approximately 10% to 15% of Caucasians and African Americans are homozygous for the TA7 repeat (*28/*28), and these individuals have a 50% higher risk of experiencing severe (grade 4 or 5) neutropenia following the administration of irinotecan. Approximately 40% of individuals treated with irinotecan are heterozygous for the TA7 repeat polymorphism (ie, TA6/TA7 or *1/*28). These individuals are also at increased risk of grade 4 neutropenia. Recently, the drug labeling for irinotecan has been changed to indicate that individuals homozygous or heterozygous for polymorphisms present in the TATA box of the UGT1A1 promoter have a higher risk for severe or life-threatening neutropenia. It appears that the risk is greatest for individuals who receive irinotecan once every 3 weeks.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
An interpretive report will be provided.
Drug-drug interactions must be considered when predicting the UGT1A1 phenotype, especially in individuals heterozygous for the TA7 polymorphism (see Cautions).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not detect polymorphisms other than *1, *28, *36, and *37. Numerous polymorphisms and rare mutations have been described that impair UGT1A1 activity. Sequencing of the full gene is also available, order UGTI/89397 UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene Sequencing, Irinotecan Hypersensitivity for situations where patients are to be evaluated for Irinotecan toxicity. Order UGT2/89611 UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene Sequencing, Hyperbilirubinemia, if testing for Gilbert Syndrome or Crigler-Najjar Syndromes is desired.
Liver or renal dysfunction may result in adverse drug reactions with irinotecan independently of TA-repeat polymorphisms.
Drugs that significantly inhibit cytochrome P450 3A4, such as ketoconazole, increase patient exposure to irinotecan and its active metabolite SN-38, potentially causing or increasing the severity of an adverse drug reaction. The drug labeling should be consulted for additional information.
Drugs that induce the overexpression of cytochrome P450 3A4, including anticonvulsant medications (such as phenytoin, phenobarbital, and carbamazepine) and rifampin, will cause substantial reduction in exposure to irinotecan and its active metabolite SN-38. The drug labeling should be consulted for changes to the use of other medications.
Herbal supplements that induce the overexpression of cytochrome P450 3A4 such as St. John's Wort, will cause substantial reduction in exposure to irinotecan and its active metabolite SN-38. The drug labeling should be consulted for changes to the use of other medications.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Innocenti F, Grimsley C, Das S, et al: Haplotype structure of the UDP-glucuronosyltransferase 1A1 promoter in different ethnic groups. Pharmacogenetics 2002;12:725-733
2. Goetz MP, Safgren S, Goldberg RM, et al: A phase I dose escalation study of irinotecan (CPT-11), oxaliplatin (Oxal), and capecitabine (Cap) within three UGT1A1 TA promoter cohorts (6/6, 6/7, and 7/7). ASCO 2005; ASCO Annual Meeting Abstract No:2014
3. Drug package insert: NDA 20-571/S-024/S-027/S-028. Camptosar (Irinotecan HCL) Final Label. Pfizer Inc, NY, rev 7/05
Method Description Describes how the test is performed and provides a method-specific reference
The promoter of UGT1A1 is amplified by PCR. The number of TA repeats is determined in the amplified product by fragment size analysis following capillary electrophoresis. (Baudhuin L, Highsmith WE, Skierka J, et al: Comparison of three methods for genotyping the UGT1A1 TA repeat polymorphism. Clin Biochem 2007:40:710-717)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Wednesday, Friday; Varies
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81350-UGT1A1 (UDP glucuronosyltransferase 1 family, polypeptide AI) (eg, irinotecan metabolism), gene analysis, common variants (eg, *28, *36, *37)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 26615 | TA/TA | In Process |
| 83949 | UGT1A1 TA Repeat Genotype | In Process |
| 26616 | Reviewed by | In Process |
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