*Includes all controls.

Irinotecan Toxicity and UGT1A1 Genotype

Uridine diphosphate-glucuronyl transferase 1A1 (UGT1A1) is an enzyme that catalyzes the glucuronidation of various compounds, including steroid hormones, bilirubin, as well as xenobiotics, such as irinotecan. This process converts these substances to more water-soluble compounds that can be eliminated from the body. A polymorphic variation in the promoter of UGT1A1 leads to decreased expression of UGT1A1, resulting in reduced glucuronidation of SN-38, the active metabolite of irinotecan. Patients with a (TA)7 repeat (UGT1A1*28) have a 12-50% increased risk of Grade 4 neutropenia or severe diarrhea.3,4 Individuals that are homozygous for UGT1A1*28 mutation, that is have two alleles with 7 TA repeats (7/7 homozygous) also known as a Gilbert’s syndrome, will have the most severe toxicity to irinotecan.

Testing Procedure and Analysis

The UGT1A1 Genotyping Kit is a polymerase chain reaction (PCR)-based assay that uses allele-specific probes to identify the most common Irinotecan polymorphic variant. The testing procedure involves three (3) simple steps:

• Isolation of DNA from whole blood
• Amplification of regions of the UGT1A1 gene using allele-specific probes
• Analysis using real-time PCR instrument software

This test can be completed in approximately 2 hours from isolation of DNA to test result.

Equipment and Materials

The UGT1A1 Genotyping Kit requires a real-time PCR instrument. Columns and reagents for DNA isolation are not included.

Intended Use

The UGT1A1 Genotyping Kit is available for Research Use Only (RUO) in the United States and for In Vitro Diagnostic use (CE-IVD) in Europe.