The clinical application of UGT1A1pharmacogenetic testing: Gene-environment interactions

Table 1 Clinical relevance of testing for the presence of UGT1A1*28

Drug	UGT1A1	Ref.	Summary	Indication for pharmacogenetic testing	Rationale
Irinotecan (SN-38)	Substrate	14-16	The presence of the UGT1A1*28 allele is a risk factor for the development of adverse reactions to irinotecan treatment	****	Testing prevents drug toxicity at high dose
Raloxifene	Substrate	17	Patients under raloxifene treatment that are homozygous for UGT1A1*28 are more exposed to its active metabolite, exhibiting a superior increase in hip bone mineral density	**	Testing could identify patients that need a higher dose of raloxifene
Raltegravir	Substrate	18,19	Homozygosity for UGT1A1*28 is correlated with an increase in raltegravir plasma concentrations, but does not seem to affect the safety profile of this drug	*	Testing does not seem to be useful
Indinavir	Inhibitor	4,20,23,26	Indinavir raises unconjugated and total bilirubin concentrations by inhibiting UGT1A1. This effect can lead to clinical jaundice in patients with the UGT1A1*28 genotype	**	Testing could help avoid hyperbilirubinaemia
Atazanavir	Inhibitor	20-22	Atazanavir inhibits the UGT1A1 enzyme, which leads to hyperbilirubinaemia. Patients with the UGT1A1*28 genotype are at greater risk of developing clinical jaundice when taking this drug	***	Strong evidence that testing may prevent clinical jaundice
Sorafenib	Inhibitor	24,25	Sorafenib at high doses inhibits UGT1A1 activity, which can cause hyperbilirubinaemia	**	Further studies are required to understand sorafenib's influence on UGT1A1 activity

*Testing does not seem necessary to guide treatment.
**Testing may be relevant to guide treatment, but further studies are required.
***There is some evidence that testing may be an important indicator to guide treatment.
****There is a strong evidence that testing provides essential information to guide treatment.

ISSN: 1479-7364