title: Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain.
abstract: OBJECTIVE
  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.
authors.affiliation: Pain Therapy Service, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: De Gregori
authors.forename: Giulia
authors.initials: G
authors.lastname: Garbin
authors.forename: Simona
authors.initials: S
authors.lastname: De Gregori
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Minella
authors.forename: Dario
authors.initials: D
authors.lastname: Bugada
authors.forename: Antonella
authors.initials: A
authors.lastname: Lisa
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Allegri
authors.forename: Guglielmina N
authors.initials: GN
authors.lastname: Ranzani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010149:Postoperative Pain / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine; D002394:Catechol O-Methyltransferase; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase