title: Catechol-o-methyltransferase polymorphisms predict opioid consumption in postoperative pain.
abstract: BACKGROUND
  Previous studies have associated the catechol-O-methyltransferase (COMT) enzyme rs4680 polymorphism with opioid consumption in the treatment of chronic cancer pain. In this study, we evaluated the association between COMT rs4680 and rs4818 polymorphisms and opioid consumption in the acute postoperative period after a nephrectomy.
  
  
  METHODS
  Opioid consumption and pain scores were evaluated in 152 patients for 48 hours after nephrectomy. The genotype of each patient was determined using polymerase chain reaction on DNA extracted from blood samples. The association between rs4680 and rs4818 genotypes and opioid consumption was evaluated using general linear model regression analysis. All P values and confidence intervals were Bonferroni corrected for the 3 comparisons among genotypes.
  
  
  RESULTS
  In the 24-hour period after surgery (COMT rs4680), patients homozygous for the variant Val/Val consumed 36% (95% confidence interval, 31%-41%) more opioids than patients homozygous for the Met/Met group (P = 0.009). No statistically significant differences among the 3 genotype groups were noted for pain scores or emesis medication use in the first 24 hours after surgery. There was a statistically significant increase in emesis medication use in patients possessing the CC genotype of rs4818 when compared to patients carrying the GG genotypes (P = 0.035). In the 6- to 48-hour postsurgery period, there was significantly higher opioid consumption in the high-activity homozygotes Val/Val than in the homozygous Met/Met group for COMT rs4680 (0-6 h: P = 0.005; 0-12 h: P = 0.015; 0-24 h: P = 0.015; and 0-48 h: P = 0.023). Patients in the homozygous GG group COMT rs4818 single nucleotide polymorphism showed statistically significant differences in opioid consumption in the first 6 hours after nephrectomy compared with heterozygous CG patients (P = 0.02).
  
  
  CONCLUSIONS
  The genetic variant of the COMT rs4680 single nucleotide polymorphism is associated with variability in opioid consumption in postoperative nephrectomy patients. The COMT rs4818 polymorphism may prove useful in predicting emesis medication use postoperatively.
authors.affiliation: From the Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami School of Medicine, Miami, Florida.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Candiotti
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: Buric
authors.forename: Kris
authors.initials: K
authors.lastname: Arheart
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yiliam
authors.initials: Y
authors.lastname: Rodriguez
authors.forename: Melvin C
authors.initials: MC
authors.lastname: Gitlin
authors.forename: Enisa
authors.initials: E
authors.lastname: Carvalho
authors.forename: Isabel
authors.initials: I
authors.lastname: Jaraba
authors.forename: Liyong
authors.initials: L
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000009:adverse effects; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; D002394:Catechol O-Methyltransferase; D005283:Fentanyl