UGT1A1 Genotyping

UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The UGT1A1 gene encodes a hepatic enzyme responsible for the conjugation of bilirubin. It also acts on the active metabolite of chemotherapeutic agents including irinotecan (Camptosar®) which is the main source of treatment-related toxicity. [65]

About 10% of the US population are poor metabolizers, which may lead to increased drug levels and high risk for toxicity from select medications that inhibit or are inactivated by UGT1A1. The frequency of carriers of a non-functional UGT1A1 allele varies among ethnicities, being highest in those of African (43%) or European (39%) descent and lowest in those of Asian (16%) descent. [66]

Indications for Testing

Patients who are candidates for UGT1A1 testing are those being considered for treatment with oncology drugs including irinotecan (Camptosar®), Belinostat (Beleodaq®), Nilotinib (Tasigna®), Pazopanib (Votrient®), those with suspected Gilbert’s syndrome or those with elevated serum bilirubin.