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

Manuela De Gregori, Giulia Garbin, Simona De Gregori, Cristina E. Minella, Dario Bugada, Antonella Lisa, Stefano Govoni, Mario Regazzi, Massimo Allegri, Guglielmina N. Ranzani

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1651-1658
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume69
Issue number9
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Acute Pain
Postoperative Pain
Morphine
Analgesics
Haplotypes
Patient-Controlled Analgesia
Genotype
Pain
Valine
Adenine
Reverse-Phase Chromatography
DNA Sequence Analysis
Methionine
Mass Spectrometry
Pharmacokinetics
High Pressure Liquid Chromatography
DNA

Keywords

  • Genetic polymorphisms
  • Morphine consumption
  • Pharmacokinetics
  • Postoperative pain

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain. / De Gregori, Manuela; Garbin, Giulia; De Gregori, Simona; Minella, Cristina E.; Bugada, Dario; Lisa, Antonella; Govoni, Stefano; Regazzi, Mario; Allegri, Massimo; Ranzani, Guglielmina N.

In: European Journal of Clinical Pharmacology, Vol. 69, No. 9, 09.2013, p. 1651-1658.

Research output: Contribution to journalArticle

De Gregori, Manuela ; Garbin, Giulia ; De Gregori, Simona ; Minella, Cristina E. ; Bugada, Dario ; Lisa, Antonella ; Govoni, Stefano ; Regazzi, Mario ; Allegri, Massimo ; Ranzani, Guglielmina N. / Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain. In: European Journal of Clinical Pharmacology. 2013 ; Vol. 69, No. 9. pp. 1651-1658.
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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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T1 - Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain

AU - De Gregori, Manuela

AU - Garbin, Giulia

AU - De Gregori, Simona

AU - Minella, Cristina E.

AU - Bugada, Dario

AU - Lisa, Antonella

AU - Govoni, Stefano

AU - Regazzi, Mario

AU - Allegri, Massimo

AU - Ranzani, Guglielmina N.

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - Genetic polymorphisms

KW - Morphine consumption

KW - Pharmacokinetics

KW - Postoperative pain

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