UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease

Am J Hematol. 2008 Mar;83(3):200-2. doi: 10.1002/ajh.21051.


The purpose of the study was to determine if UDP-glucuronosyltransferase (UGT) 2B7 allelic variants encoding for UGT2B7, primary enzyme responsible for morphine glucuronidation contribute to the variability in the hepatic clearance of morphine in sickle cell disease (SCD). Twenty-four hour PK study of morphine and UGT2B7 variants genotyping was performed in 20 SCD patients in a steady state of health. Presence of the -840G allele (GG and GA) was associated with lower morphine metabolites/morphine AUC ratio compared with AA genotype (1.8 +/- 0.5 vs. 3.0 +/- 1.8 for M6G/M and 10.1 +/- 2.7 vs. 15.7 +/- 9.4 for M3G/M) (P = 0.03). Presence of UGT2B7 -840G allele is associated with significantly reduced glucuronidation of morphine and thus contributes to the variability in hepatic clearance of morphine in SCD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia, Sickle Cell / genetics*
  • Anemia, Sickle Cell / metabolism
  • Area Under Curve
  • Cross-Sectional Studies
  • Genetic Variation*
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Humans
  • Liver / metabolism*
  • Liver Function Tests
  • Metabolic Clearance Rate
  • Morphine / pharmacokinetics*
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*


  • Morphine
  • UGT2B7 protein, human
  • Glucuronosyltransferase