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1: Am J Hematol. 2008 Mar;83(3):200-2.Click here to read Links

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

Darbari DS, van Schaik RH, Capparelli EV, Rana S, McCarter R, van den Anker J.

Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC 20010, USA. ddarbari@cnmc.org

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. (c) 2007 Wiley-Liss, Inc.

PMID: 17724700 [PubMed - indexed for MEDLINE]