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.

dx.doi.org/10.1002/ajh.21051, hdl.handle.net/1765/29651
American Journal of Hematology
Erasmus MC: University Medical Center Rotterdam

Darbari, D.S, van Schaik, R.H.N, Capparelli, E.V, Rana, S, McCarter, R, & van den Anker, J.N. (2008). UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease. American Journal of Hematology, 83(3), 200–202. doi:10.1002/ajh.21051