title: 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.affiliation: Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC 20010, USA. ddarbari@cnmc.org
authors.forename: Deepika S
authors.initials: DS
authors.lastname: Darbari
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: Sohail
authors.initials: S
authors.lastname: Rana
authors.forename: Robert
authors.initials: R
authors.lastname: McCarter
authors.forename: John
authors.initials: J
authors.lastname: van den Anker
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000378:metabolism; D019540:Area Under Curve; D003430:Cross-Sectional Studies; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase