Test utility

Identifying individuals increased risk of toxicity with drugs that are metabolized by UGT1A1, including irinotecan and atazanavir.

Establishing a diagnosis of Gilbert syndrome.

Clinical significance

Uridine diphosphate-glucuronyl transferase 1A1 (UGT1A1) is an enzyme that catalyzes the glucuronidation of various compounds, such as steroids, bilirubin, hormones, and drugs.

A polymorphism in the promoter region of UGT1A1 gene leads to reduced expression of UGT1A1, leading to decreased glucuronidation of SN-38, the active metabolite of irinotecan. Patients carrying one or two copies of the TA7 repeat (*28) have an increased risk of toxicity such as neutropenia and diarrhea.

Reduced hepatic UGT1A1 activity to 30% of normal is an indication of Gilbert syndrome. Genotypes most commonly implicated in Gilbert syndrome are UGT1A1*28/*28 and UGT1A1*6/*6.

Genes/Alleles tested

UGT1A1 *1 (TA6), *6, *27, *28 (TA7), *36 (TA5), *37 (TA8), *80

Methodology

Sanger sequencing

CPT Code

81350