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Influence of UGT2B7, OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption
Unit for Development and Patient Safety, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Anesthesia and Intensive Care, Örebro University, Örebro, Sweden.ORCID iD: 0000-0001-6128-7752
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Unit for Development and Patient Safety, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden .
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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 autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24hr after initiation of analgesia through a patient-controlled analgesia (PCA) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies 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. The 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 concentrations observed in individual patients.

Place, publisher, year, edition, pages
2014. Vol. 115, no 5, 423-431 p.
National Category
Pharmacology and Toxicology
Research subject
Pharmaceutical Pharmacology
Identifiers
URN: urn:nbn:se:oru:diva-39454DOI: 10.1111/bcpt.12248ISI: 000344015300008PubMedID: 24703092Scopus ID: 2-s2.0-84900628888OAI: oai:DiVA.org:oru-39454DiVA: diva2:770368
Note

Funding Agencies:

Swedish Academy of Pharmaceutical Sciences (SAPS)

National Board of Health and Welfare in Sweden

County Council of Östergotland

Available from: 2014-12-10 Created: 2014-12-10 Last updated: 2016-12-05Bibliographically approved

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