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

Abstract

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.

• Authors: Deepika S Darbari, Ron H N van Schaik, Edmund V Capparelli, Sohail Rana, Robert McCarter, John van den Anker
• Journal: American journal of hematology (Am J Hematol) Vol. 83 Issue 3 Pg. 200-2 (Mar 2008) ISSN: 0361-8609 [Print] United States
• PMID: 17724700 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Morphine
• UGT2B7 protein, human
• Glucuronosyltransferase

Topics

• Anemia, Sickle Cell (genetics, 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