Test Code UGT1 UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene Sequencing, Varies
Advisory Information
Shipping Instructions
If submitting microtube, place inside a larger tube or vial for transport.
Specimen Required
Multiple whole blood EDTA 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.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Adults: Lavender top (EDTA)
Pediatrics: Purple microtube
Specimen Volume:
Adults: 3 mL
Pediatrics: 1 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Container/Tube: Saliva Swab Collection Kit
Specimen Volume: One swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Specimen Type: DNA
Container/Tube: 2 mL screw top tube
Specimen Volume: 100 mcL (microliters)
Collection Instructions:
1. The preferred volume is 100 mcL at a concentration of 50 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. UGT1A1 Gene Testing Patient Information (T664) is requested but not required. See Special Instructions.
3. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Oncology Test Request (T729)
-Therapeutics Test Request (T831)
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
Identifying individuals who are at risk of hyperbilirubinemia
Follow-up testing for individuals with a suspected UGT1A1 variant, who had negative TA repeat region testing
Establishing a diagnosis of Gilbert, Crigler-Najjar syndrome type I or type II
Establishing carrier status for Gilbert, Crigler-Najjar syndrome type I or type II
Special Instructions
Method Name
Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis
Reporting Name
UGT1A1 Full Gene SequencingSpecimen Type
VariesSpecimen Minimum Volume
Blood: 0.45 mL
Saliva: one swab
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Varies |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability. |
Clinical Information
The UGT1A1 gene is part of a gene complex located on chromosome 2 that encodes several enzymes called uridine diphosphate (UDP)-glycuronosyl transferases. These enzymes perform a chemical reaction called glucuronidation, a major pathway that enhances the elimination of small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble metabolites that can be excreted from the body.
The UGT1A1 enzyme, primarily found in the liver, is responsible for the gluronidation of bilirubin, converting it from the toxic form of bilirubin (unconjugated bilirubin) to its nontoxic, water-soluble form (conjugated bilirubin). Genetic variants in UGT1A1 may cause reduced or absent UGT1A1 enzymatic activity, resulting in conditions associated with unconjugated hyperbilirubinemia including Gilbert syndrome and Crigler-Najjar syndromes types I and II.
Gilbert syndrome is the most common hereditary cause of increased bilirubin and is characterized by total serum bilirubin levels of 1 to 6 mg/dL. Gilbert syndrome is generally considered to be an autosomal recessive disorder, although autosomal dominant inheritance has been suggested in some cases.(1) Gilbert syndrome is caused by a 25% to 50% reduction in glucuronidation activity of the UGT1A1 enzyme and is characterized by episodes of mild intermittent jaundice and the absence of liver disease.
Crigler-Najjar syndromes types I and II (CN1 and CN2) are autosomal recessive disorders caused by more severe reductions in UGT1A1 glucuronidation activity. CN1 is the most severe form, with complete absence of enzyme activity and total serum bilirubin levels of 20 to 45 mg/dL. Infants with CN1 present with jaundice shortly after birth that persists thereafter.(2) CN2 is milder than CN1, with at least partial UGT1A1 activity and total serum bilirubin ranging from 6 to 20 mg/dL. Phenobarbital, a drug that induces synthesis of a number of hepatic enzymes, is effective in decreasing serum bilirubin levels by approximately 25% in patients with CN2; CN1 does not respond to phenobarbital treatment. If left untreated, the buildup of bilirubin in a newborn can cause bilirubin-induced brain damage, known as kernicterus. In addition to phenobarbital, treatments of CN may include: phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate, and liver transplantation.
In addition to the role of UGT1A1 in bilirubin metabolism, this enzyme also plays a role in the metabolism of several drugs. 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.(3,4)
Additional drugs have also been associated with an increased risk for adverse outcomes in patients with 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 variants 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. In this assay, the promoter, exons, and exon-intron boundaries are assessed for variants.(5)
Reference Values
An interpretive report will be provided.
Day(s) and Time(s) Performed
Tuesday; 8 a.m.
Analytic Time
7 days (Not reported on Saturday or Sunday)Performing Laboratory

Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
81404
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
UGTFG | UGT1A1 Full Gene Sequencing | 93844-9 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
91972 | Result Summary | 50397-9 |
91977 | TA Repeat Result | 95143-4 |
BA0266 | Full Gene Sequence Result | 82939-0 |
91993 | Interpretation | 69047-9 |
92007 | Additional Information | 48767-8 |
92008 | Method | 49549-9 |
92009 | Disclaimer | 62364-5 |
92010 | Reviewed By | 18771-6 |
NY State Approved
YesTesting Algorithm
See UGT1A1 Test-Ordering Algorithm in Special Instructions.
Computer Interface Code
PDM # 1759385