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Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients

The Pharmacogenomics Journal volume 3, pages 17–26 (2003)Cite this article

A Corrigendum to this article was published on 20 August 2003

ABSTRACT

We have screened a cohort of 239 Norwegian cancer patients for sequence variation in the coding and regulatory regions of the UDP-glucuronosyltransferase 2B7 gene (UGT2B7) and analyzed the impact of gene variants on morphine glucuronidation in vivo. In all, 12 single nucleotide polymorphisms (SNPs) were identified, 10 of which have not been previously described. Only one SNP causes a change in amino acid sequence (H268Y). Seven UGT2B7 genotypes were observed and three main haplotypes predicted. There was no correlation between UGT2B7 genotype or haplotype and morphine glucuronide to morphine serum ratios among 175 patients who received chronic oral morphine therapy, and who had normal renal and hepatic function. The apparent lack of functional polymorphisms fits well with the near unimodal, but broad, distributions of the ratios (morphine 3-glucuronide/morphine: 6.4–309.2; morphine 6-glucuronide/morphine: 0.5–72.8). Our results suggest that factors other than UGT2B7 polymorphism may be more deciding for the variability in morphine glucuronide to morphine serum ratios.

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Acknowledgements

We are grateful to the patients who participated in this study. We thank the staff at the Department of Clinical Pharmacology, St Olav's University Hospital, for doing the morphine and morphine metabolite analyses, Ruth Krokan for operating the DNA sequence analyzer, and Dr Petter C Borchgrevink and Dr Ola Dale for valuable discussion. This work was supported by grants from the Research Council of Norway.

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Authors and Affiliations

  1. Institute of Cancer Research and Molecular Biology, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    M Holthe, T N Rakvåg, J R Idle, H E Krokan & F Skorpen

  2. Department of Anesthesia and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    P Klepstad

  3. Department of Environmental Medicine, Unit for Applied Clinical Research, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    P Klepstad & S Kaasa

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  1. M Holthe
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Correspondence to F Skorpen.

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Holthe, M., Rakvåg, T., Klepstad, P. et al. Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients. Pharmacogenomics J 3, 17–26 (2003). https://doi.org/10.1038/sj.tpj.6500139

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