liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Influence of UGT2B7, OPRM1 and ABCB1 gene polymorphisms on morphine use
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Department of Anesthesia and Intensive Care, Örebro University, Örebro, Sweden.
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden .
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Show others and affiliations
2014 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 115, no 5, 423-431 p.Article in journal (Refereed) Published
Abstract [en]

Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in, both, effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7, OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsy cases as morphine is also a very commonly abused drug

Blood samples were collected from 40 patients following abdominal hysterectomy, 24 hours after initiation of analgesia through a PCA pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsy cases found positive for morphine in routine forensic analysis.

Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. Dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood.

Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients.

We conclude that gene polymorphisms contribute significantly to the variation in morphine levels observed in individual patients.

Place, publisher, year, edition, pages
Wiley , 2014. Vol. 115, no 5, 423-431 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-96791DOI: 10.1111/bcpt.12248ISI: 000344015300008PubMedID: 24703092OAI: diva2:643355
Available from: 2013-08-27 Created: 2013-08-27 Last updated: 2016-02-22Bibliographically approved
In thesis
1. Practical and clinical use of opioids
Open this publication in new window or tab >>Practical and clinical use of opioids
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pain is a common symptom of a number of conditions including cancer and one of the most frequent reasons for seeking healthcare. Acute and chronic pain result in considerable discomfort with a detrimental impact on the quality of life. Opioids are the mainstay of pain management for many patients with severe pain. Opioids are, unfortunately, also commonly abused drugs, and are well-represented in forensic toxicology investigations.

Side effects related to the central nervous system are the major reasons fordiscontinuation of opioid treatment. In this thesis, we tested the hypothesis that local analgesic treatment by opioids, without the usual opioid-related side effects, could be a potential alternative to systemic opioid treatment. We examined the analgesic effect of topically applied morphine in a randomized, double blind, cross over study in patients with painful leg ulcers. Significant reduction of pain was obtained after application of both morphine and placebo gel. Morphine reduced pain more than placebo but the difference was not statistically significant. However, morphine could reduce pain considerably more than placebo in those cases where VAS (Visual analog scale) was higher initially.

Another issue with opioid therapy is the substantial individual variability in response to opioids including morphine and tramadol. We investigated the significance of UGT2B7, CYP2D6, OPRM1 and ABCB1 polymorphisms for pharmacokinetic and pharmacodynamic properties of morphine and tramadol. We showed that genetic variants in CYP2D6 and UGT2B7 have an important role in the metabolism of tramadol and morphine respectively. While the role of SNPs in ABCB1 remained unclear, genetic variants in OPRM1 gene were correlated with the required dose of morphine. Taken together, these findings suggest that genotypes should be taken into consideration when interpreting clinical pharmacology and forensic toxicology results.

Opioids, besides their analgesic properties, have other pharmacological effects including effects on immune system. We evaluated potential differences between commonly used opiates with regard to their effect on the immune system. We found an inhibition of cytokine release, in the order of potency as follows: tramadol > ketobemidone >morphine >fentanyl. All opioids with the exception of fentanyl were capable of inhibiting production of mRNAs for TNF-alpha and IL-8. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of opioids and to improve opioid treatment strategies in patients with cancer.

Here, we have found that individual genotype matters and affects the individual response. Further research is warranted to tailor individualized treatment. Personalized medicine has increased in importance and will hopefully in the near future become standard procedure to improve and predict the outcome of treatment by opioids.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 72 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1364
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-96795 (URN)978-91-7519-603-9 (print) (ISBN)
Public defence
2013-09-13, Berzeliussalen,, Campus US, Linköpings universitet, Linköping, 13:00 (English)

The series name in the title page is incorret. The correct title should be Linköping University Medical Dissertations.

Available from: 2013-08-27 Created: 2013-08-27 Last updated: 2014-06-05Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Bastami, SalumehZackrisson, Anna LenaAhlner, JohanOsman, AbdimajidUppugunduri, Srinivas
By organisation
Division of Drug ResearchFaculty of Health SciencesDivision of Microbiology and Molecular MedicineDepartment of Clinical Chemistry
In the same journal
Basic & Clinical Pharmacology & Toxicology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 243 hits
ReferencesLink to record
Permanent link

Direct link