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

Eur J Clin Pharmacol (2013) 69:16511658 DOI 10.1007/s00228-013-1523-7

PHARMACOGENETICS

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

Received: 20 December 2012 /Accepted: 24 April 2013 /Published online: 19 May 2013 # Springer-Verlag Berlin Heidelberg 2013

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

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.

M. De Gregori : C. E. Minella : D. Bugada : M. AllegriPain Therapy Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

G. Garbin : G. N. Ranzani (*)

Department of Biology and Biotechnology, University of Pavia, Via Ferrata 1,27100 Pavia, Italye-mail: [email protected]

S. De Gregori : M. RegazziUnit of Clinical Pharmacokinetics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy

A. LisaInstitute of Molecular Genetics of the Italian National Research Council, Pavia, Italy

S. GovoniDepartment of Drug Sciences, Pharmacology Section, University of Pavia, Pavia, Italy

M. AllegriDepartment of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

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 homo-zygous 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...