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.

journal_name

Am J Hematol

authors

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

doi

10.1002/ajh.21051

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

200-2

issue

3

eissn

0361-8609

issn

1096-8652

journal_volume

83

pub_type

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