Variability in UDP-glucuronosyltransferase genes and morphine metabolism: Observations from a cross-sectional multicenter study in advanced cancer patients with pain

Torill Fladvad, Pål Klepstad, Mette Langaas, Ola Dale, Stein Kaasa, Augusto Caraceni, Frank Skorpen

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: The objective of the present study was to determine whether genetic variability in UDP-glucuronosyltransferase (UGT) genes, together with clinical factors, contribute to variability in morphine glucuronide (M6G and M3G) to morphine serum concentration ratios in patients with advanced cancer receiving chronic morphine therapy. MATERIALS AND METHODS: A total of 41 polymorphisms and predicted haplotypes in the UGT2B7, UGT1A1, and UGT1A8 genes were analyzed in 759 patients who were recruited from the European Pharmacogenetic Opioid Study and received chronic morphine therapy by the oral route (n=635) or parenterally (n=124). The administration groups were analyzed separately by multiple linear regression analyses. RESULTS: Two haplotypes in UGT1A1/UGT1A8 were weak predictors of reduced M6G/morphine and M3G/morphine serum ratios after oral administration (false discovery rate-corrected P-values

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalPharmacogenetics and Genomics
Volume23
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Keywords

  • morphine
  • morphine-3-glucuronide
  • morphine-6-glucuronide
  • polymorphism
  • UDP-glucuronosyltransferase

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

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