Genetic polymorphisms of UDP-glucuronosyltransferase and their functional significance

    Research output: Contribution to journalMeeting Abstractpeer-review

    Abstract

    Conjugation with glucuronic acid is responsible for the elimination of a diverse range of xenobiotics and endogenous compounds. Glucuronidation reactions are catalysed by the
    microsomal enzyme UDP-glucuronosyltransferase (UGT). Consistent with its broad substrate profile, UGT is known to exist as a superfamily of enzymes. Sixteen functional human UGT genes have been identified to date, and these have been classified into two families, UGT1 and UGT2 based on evolutionary divergence. Although it is probable that all UGT genes exhibit polymorphic variation in their coding and regulatory regions, genetic polymorphisms have been described to date for only six human enzymes; UGT1, 1A1, 1A6, 1A7, 2B4, 2B7 and 2B15. Ethnic differences commonly occur in the frequencies of allelic variants. However, the majority of the known UGT genetic polymorphisms appear to be of minimal functional significance, probably as a consequence of the overlapping substrate specificities of UGTs. Important exceptions are the polymorphisms associated with UGT1A1, the principal form involved in bilirubin glucuronidation. Three types of inheritable unconjugated hyperbilirubinemias arise from numerous mutant UGT1A1 alleles or a UGT1A1 promoter polymorphism. Recent evidence also suggests that homozygosity for the lower activity allele of UGT2B15, which contributes to androgen glucuronidation, may be a risk factor for the development of prostate cancer.
    Original languageEnglish
    Pages (from-to)33-33
    Number of pages1
    JournalToxicology
    Volume164
    Issue number1-3
    DOIs
    Publication statusPublished - 8 Jul 2001
    Event39th Society of Toxicology Annual Meeting - Philadelphia Convention Center, Philadelphia, United States
    Duration: 19 Mar 200023 Mar 2000

    Fingerprint

    Dive into the research topics of 'Genetic polymorphisms of UDP-glucuronosyltransferase and their functional significance'. Together they form a unique fingerprint.

    Cite this