The clinical application of UGT1A1 pharmacogenetic testing: gene-environment interactions.
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Marques SC, Ikediobi ON
The clinical application of UGT1A1 pharmacogenetic testing: gene-environment interactions.
Hum Genomics. 2010 Apr;4(4):238-49. doi: 10.1186/1479-7364-4-4-238.
- PubMed ID
- 20511137 [ View in PubMed]
- Abstract
Over the past decade, the number of pharmacogenetic tests has increased considerably, allowing for the development of our knowledge of their clinical application. The uridine diphosphate glucuronosyltransferase 1A1 gene ( UGT1A1 ) assay is an example of a pharmacogenetic test. Numerous variants have been found in UGT1A1 , the main conjugating enzyme of bilirubin and drugs such as the anticancer drug irinotecan. Recently, the US Food and Drug Administration (FDA) recommended testing for the presence of UGT1A1*28 , an allele correlated with decreased transcriptional activity, to predict patients at risk of irinotecan toxicity. The administration of other drugs - such as inhibitors of the UGT1A1 enzyme - can clinically mimic the *28 phenotype, whereas inducers of UGT1A1 can increase the glucuronidation rate of the enzyme. The *28 polymorphism is not present in all ethnicities at a similar frequency, which suggests that it is important to study different populations to determine the clinical relevance of testing for UGT1A1*28 and to identify other clinically relevant UGT1A1 variants. Environmental factors such as lifestyle can also affect UGT1A1 activity. This review is a critical analysis of studies on drugs that can be affected by the presence of UGT1A1*28 , the distribution of this polymorphism around the globe, distinct variants that may be clinically significant in African and Asian populations and how lifestyle can affect treatment outcomes that depend on UGT1A1 activity.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Atazanavir UDP-glucuronosyltransferase 1-1 Protein Humans NoInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbacavirNelfinavir The metabolism of Abacavir can be increased when combined with Nelfinavir. AbacavirPhenytoin The metabolism of Abacavir can be increased when combined with Phenytoin. AbacavirDesogestrel The metabolism of Abacavir can be increased when combined with Desogestrel. AbacavirLamotrigine The metabolism of Abacavir can be increased when combined with Lamotrigine. AbacavirEfavirenz The metabolism of Abacavir can be increased when combined with Efavirenz.