Skip to main content

UDP glucuronosyltransferase 2B7 single nucleotide polymorphism (rs7439366) influences heat pain response in human volunteers after i.v. morphine infusion

Introduction

Morphine remains the most widely used intravenous opioid in the perioperative setting worldwide. Maintaining therapeutic CNS concentrations of many opioids is confounded by considerable variability in disposition. Recent findings indicate a role for the UGT2B7 expressed in the liver, for variability of substrate effects. This phenomenon is attributed to genetic and environmental factors. However, evidence for effect variation due to UGT2B7-mediated glucuronization of morphine in humans is lacking.

Methods

We tested the hypothesis that variations of morphine effects could be explained in part by genetic variation in the UGT2B7 gene by pupil diameter change and heat pain response in 35 healthy volunteers, who were given 0.2 mg/kg morphine i.v. over 2 hours. This abstract reports the results for the UGT2B7 (rs7439366) SNP on chromosome 4, coding for a histidine or a tyrosine at position 268, resulting in decreased enzyme activity.

Results

Ten subjects exhibited the wildtype, 20 were heterozygous and five were homozygous carriers of the allele. Peak effects of miosis did not differ for the three variants (Figure 1). However, while the results for heat pain response indicate almost no effect at all for wildtype subjects, carriers of the T allele experience a higher peak and an extended analgesia (Figure 2). Neither the parent drug nor the 3-glucuronide and 6-glucuronide serum concentrations differed significantly among the research subjects.

Figure 1
figure1

Miosis (mm) after the start of the morphine injection.

Figure 2
figure2

Maximally tolerable temperatures (°C) hours after morphine injection.

Conclusions

While morphine effects might be influenced in part by UGT2B7 genotype, there is a differential effect on pupil contractility and heat pain response. This cannot be readily explained by drug or metabolite serum concentration and warrants further investigation, including different enzyme product effects on cerebral morphine levels.

Author information

Affiliations

Authors

Corresponding author

Correspondence to KM Meissner.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Meissner, K., Meyer zu Schwabedissen, H., Göpfert, C. et al. UDP glucuronosyltransferase 2B7 single nucleotide polymorphism (rs7439366) influences heat pain response in human volunteers after i.v. morphine infusion. Crit Care 15, P363 (2011). https://doi.org/10.1186/cc9783

Download citation

Keywords

  • Morphine
  • Product Effect
  • Pupil Diameter
  • Homozygous Carrier
  • Decrease Enzyme Activity