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Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms.

Methods

A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OPRM1 and UGT2B7 genes. The plasma concentration of morphine and of M3G/M6G metabolites were evaluated by means of reversed phase high-performance liquid chromatography coupled with mass spectrometry.

Results

An association between average morphine consumption during the first 24 postoperative hours by patient-controlled analgesia (PCA) and COMT haplotypes was found. Specifically, patients with the diplotype for average pain intensity (APS/APS) required the lowest morphine doses compared to the other subjects (p = 0.011). The APS haplotype contains an adenine corresponding to methionine, instead of valine, at position 158 of the COMT protein. Met/Met homozygous patients consumed significantly lower morphine doses than other subjects (p = 0.014); accordingly, Val158Met genotyping alone might be used in the clinical setting to predict PCA morphine need. Considering both COMT Val158Met and OPRM1 A118G polymorphisms, carriers of both the Met/Met and AA genotypes required less morphine than other subjects, although the difference was not significant. The analysis of UGT2B7 revealed the occurrence of two common haplotypes (G_C_C_A_C and A_T_T_G_T) that did not prove to be related with plasma morphine and M3G/M6G concentration.

Conclusions

By considering COMT, OPRM1, and UGT2B7 genotypes, as well as pharmacokinetic results, only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy.

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Conflict of interest

None.

Source of founding

IRCCS-San Matteo Hospital Foundation, Banca del Monte di Lombardia Foundation, Cariplo Foundation (grant 2010/0253)

Author information

Authors and Affiliations

  1. Pain Therapy Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

    Manuela De Gregori, Cristina E. Minella, Dario Bugada & Massimo Allegri

  2. Department of Biology and Biotechnology, University of Pavia, Via Ferrata 1, 27100, Pavia, Italy

    Giulia Garbin & Guglielmina N. Ranzani

  3. Unit of Clinical Pharmacokinetics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

    Simona De Gregori & Mario Regazzi

  4. Institute of Molecular Genetics of the Italian National Research Council, Pavia, Italy

    Antonella Lisa

  5. Department of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy

    Stefano Govoni

  6. Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

    Massimo Allegri

Authors
  1. Manuela De Gregori
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  2. Giulia Garbin
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  3. Simona De Gregori
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  4. Cristina E. Minella
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  7. Stefano Govoni
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  8. Mario Regazzi
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  9. Massimo Allegri
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  10. Guglielmina N. Ranzani
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Corresponding author

Correspondence to Guglielmina N. Ranzani.

Additional information

Manuela De Gregori, Giulia Garbin, Simona De Gregori, Cristina E. Minella, Dario Bugada, Stefano Govoni, Mario Regazzi, Massimo Allegri, Guglielmina N. Ranzani are members of SIMPAR (Study In Multidisciplinary PAin Research) group.

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De Gregori, M., Garbin, G., De Gregori, S. et al. Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain. Eur J Clin Pharmacol 69, 1651–1658 (2013). https://doi.org/10.1007/s00228-013-1523-7

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  • DOI: https://doi.org/10.1007/s00228-013-1523-7

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