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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine.

We investigated the variation in the uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) gene in patients receiving patient-controlled analgesia with morphine. UGT2B7 was sequenced in phenotypic extremes (n = 12) of the distribution of morphine-6-glucuronide/morphine plasma ratios. A new -161C/T promoter variant was in complete linkage disequilibrium with the 802C/T variant and was more frequent in low glucuronidators (P =.039). Both variants were genotyped in all patients (n = 86), and complete linkage disequilibrium was confirmed. Trend analysis showed reduced morphine-6-glucuronide/morphine ratios in patients with T/T, C/T, and C/C genotypes (T/T > C/T > C/C) (P =.031). Morphine levels were lower in T/T patients (median, 18 ng/mL [range, 18-1490 ng/mL]) as compared with C/T and C/C patients combined (median, 66 ng/m; range, 18-3995 ng/mL) (P =.04). Morphine-6-glucuronide and morphine-3-glucuronide concentrations were significantly lower in C/C patients (median, 18 ng/mL; range, 0-66 ng/mL; and median, 152 ng/mL; range, 30-434 ng/mL; respectively) compared with C/T and T/T patients combined (median, 43 ng/mL; range, 0-193 ng/mL; and median, 242 ng/mL; range, 33-1381 ng/mL; respectively) (P =.045 and P =.004, respectively). Interindividual differences in morphine glucuronidation may be the result of genetic variation in UGT2B7, and further studies are indicated.[1]

References

  1. A pharmacogenetic study of uridine diphosphate-glucuronosyltransferase 2B7 in patients receiving morphine. Sawyer, M.B., Innocenti, F., Das, S., Cheng, C., Ramírez, J., Pantle-Fisher, F.H., Wright, C., Badner, J., Pei, D., Boyett, J.M., Cook, E., Ratain, M.J. Clin. Pharmacol. Ther. (2003) [Pubmed]
 
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