Variability and function of family 1 uridine-5'-diphosphate glucuronosyltransferases (UGT1A).

Abstract:

:The substrate spectrum of human UDP-glucuronosyltransferase 1A (UGT1A) proteins includes the glucuronidation of non-steroidal anti-inflammatory drugs, anticonvulsants, chemotherapeutics, steroid hormones, bile acids, and bilirubin. The unique genetic organization of the human UGT1A gene locus, and an increasing number of functionally relevant genetic variants define tissue specificity as well as a broad range of interindividual variabilities of glucuronidation. Genetic UGT1A variability has been conserved throughout the protein's evolution and shows ethnic diversity. It is the biochemical and genetic basis for clinical phenotypes such as Gilbert's syndrome and Crigler-Najjar's disease as well as for the potential for severe, unwanted drug side effects such as in irinotecan treatment. UGT1A variants influence the metabolic effects of xenobiotic exposure and therefore have been linked to cancer risk. Detailed knowledge of the organization, function, and pharmacogenetics of the human UGT1A gene locus is likely to significantly contribute to the improvement of drug safety and efficacy as well as to the provision of steps toward the goal of individualized drug therapy and disease risk prediction.

journal_name

Crit Rev Clin Lab Sci

authors

Strassburg CP,Kalthoff S,Ehmer U

doi

10.1080/10408360802374624

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

485-530

issue

6

eissn

1040-8363

issn

1549-781X

pii

905316035

journal_volume

45

pub_type

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