Sorted By Test Name - Mayo Medical Laboratories

UGTI
89397
UGTIO
60349
UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene
Sequencing, Irinotecan Hypersensitivity
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.(3,4) 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 polymorphisms and mutations in this assay.(5) More than 100 mutations have been
described in the UGT1A1 gene; 42 of the described mutations have decreased enzyme activity.
Useful For: Identifying individuals who are at increased risk of adverse drug reactions with irinotecan
and who should be considered for decreased dosing of the drug
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Guilemette C: Pharmacogenomics of human UDP-glucuronosyl-transferase
enzymes. Pharmacogenomics J 2003;3:136-158 2. 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 3. 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 4. NDA
20-571/S-024/S-027/S-028. Camptosar (Irinotecan HCL) Final Label. July 21, 2005. Pfizer 5. Kitagawa
C, Ando M, Ando Y, et al: Genetic polymorphism in the Phenobarbital-responsive enhancer module of
the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity. Pharmacogenet Genomics
2005;15:35-41
UDP-Glucuronosyl Transferase 1A1 (UGT1A1), Full Gene
Sequencing, Irinotecan Hypersensitivity, Saliva
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.(3,4) The UGT1A1 gene maps to chromosome 2q37 and
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