Test Catalog

Test ID: U1A1V    
UDP-Glucuronosyl Transferase 1A1 TA Repeat Genotype, UGT1A1, Varies

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 drugs that are metabolized by UGT1A1; especially irinotecan, but also including atazanavir, nilotinib, pazopanib, and belinostat


Identifying individuals with Gilbert syndrome due to the presence of homozygous UGT1A1*6 (c.211G->A) allele, TA7, homozygous TA8, or compound heterozygous *6, TA7 or TA8


Identifying individuals who are carriers of Gilbert syndrome due to the presence of heterozygous TA7 or TA8

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This pharmacogenomic test interrogates the thymine-adenine (TA) repeat in the TATA-box of the promoter region of UGT1A1. Repeat number may vary from 5 to 8 TA repeats, with 6 TA repeats representing the most common (normal) number of repeats. Individuals with more than 6 TA repeats may have an increased risk for adverse drug reactions to drugs metabolized by UGT1A1, especially atazanavir, irinotecan, nilotinib, pazopanib, and belinostat. Homozygosity for TA7, TA8, or compound heterozygosity for TA7/TA8 is also consistent with a diagnosis of Gilbert syndrome. Heterozygosity for TA7 or TA8 is consistent with carrier status for Gilbert syndrome. Note that this testing uses a tagging single nucleotide polymorphism (SNP) strategy for the TA5 and for the TA7 and TA8 repeats. This testing is not able to distinguish between TA7 and TA8 so when the tagging SNP is detected, TA7 is assigned. The function of genes with TA7 and TA8 repeats are thought to be the same. In addition, this test evaluates the UGT1A1*6 (c.211G->A) allele.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See UGT1A1 Test-Ordering Algorithm in Special Instructions.

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 phase II conjugation of certain drugs, like atazanavir, irinotecan, nilotinib, pazopanib, and belinostat. UGT1A1 is additionally responsible for glucuronide conjugation of bilirubin, which renders the bilirubin water soluble and permits excretion of the bilirubin-glucuronide conjugates in urine. Reduced UGT1A gene transcription due to variation in the number of thymine-adenine (TA) repeats in the TATA box of the gene promoter and c.211G->A (*6) results in reduced enzymatic activity and an increased risk for adverse outcomes in response to drugs metabolized by UGT1A1. These variants are also associated with Gilbert syndrome (unconjugated hyperbilirubinemia).


The TA repeat number may vary from 5 to 8 TA (TA5-TA8) repeats, with 6 TA (TA6) repeats being the most common allele. TA6 is the reference allele and is considered to have normal UGT1A1 expression. In addition, the rare TA5 repeat (*36: c.-41_-40delTA) has normal UGT1A1 expression. Individuals with TA7 repeat (*28: c.-41_-40dupTA) or the rare TA8 repeat (TA8 or *37: c.-43_-40dupTATA, not distinguished from TA7 with this assay) have decreased expression of UGT1A1. Approximately 10% to 15% of Caucasians and African Americans are homozygous for the TA7 repeat (*28/*28).


UGT1A1 is involved in the metabolism of irinotecan, a chemotherapy drug used to treat solid tumors including colon, rectal, and lung cancers. If UGT1A1 activity is reduced or deficient, the active irinotecan metabolite (SN-38) is less efficiently conjugated with glucuronic acid, which leads to an increased concentration of SN-38. This in turn can result in severe neutropenia; and the combination of neutropenia with diarrhea can be life-threatening. Individuals who are homozygous for *28 (TA7) 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 allele (ie, TA6/TA7 or heterozygous *28). These individuals are also at increased risk of grade 4 neutropenia. The drug label for irinotecan indicates that individuals homozygous or heterozygous for TA repeat variants have a higher risk for severe or life-threatening neutropenia. The risk is thought to be greatest in individuals who receive irinotecan once every 3 weeks.


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 atazanavir, nilotinib, pazopanib, and belinostat all contain warnings for an increased risk (incidence) of adverse outcomes in patients who have reduced activity alleles. Recently, the Clinical Pharmacogenetics Implementation Consortium (CPIC) released guidelines for atazanavir treatment that indicate patients who are homozygous for a reduced activity (decreased expression) allele should be considered for an alternate medication due to the significant risk for developing hyperbilirubinemia (jaundice).(2)


Gilbert syndrome (GS), found in 5% to 10% of the population, is the most common hereditary cause of increased bilirubin and is associated with usually benign, mild hyperbilirubinemia (bilirubin levels are typically around 3 mg/dL). Gilbert syndrome is caused by a 25% to 50% reduced glucuronidation activity of the UGT1A1 enzyme and characterized by episodes of mild intermittent jaundice and the absence of liver disease. Homozygosity for the reduced activity alleles, UGT1A1*6 (c.211G->A) allele, TA7, and TA8, or compound heterozygosity (*6, TA7, or TA8) is consistent with a diagnosis of Gilbert syndrome. Heterozygosity for *6, TA7 or TA8 is consistent with carrier status for Gilbert syndrome.

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). For additional information regarding pharmacogenomic genes and their associated drugs, see Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.


Liver or renal dysfunction may result in adverse drug reactions with irinotecan independently of thymine-adenine (TA)-repeat variants.

Clinical Reference Recommendations for 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. Gammal RS, Court MH, Haidar CE, et al: Clinical Pharmacogenomics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing. Clin Pharmacol Ther 2016 Apr;99(4):363-369

3. Shibata T, Minami Y, Mitsuma A, et al: Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia. Int J Clin Oncol 2014;19:391-396

4. U.S. Food and Drug Administration, Pharmacogenomic Biomarkers in Drug Labeling. Accessed June 2017. Available at www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm

5. UDP-Glucuronosyltransferase Alleles Nomenclature page. Accessed June 2017. Available at www.pharmacogenomics.pha.ulaval.ca/cms/ugt_alleles

Special Instructions Library of PDFs including pertinent information and forms related to the test