title: Effects of genetic polymorphisms of OPRM1, ABCB1, CYP3A4/5 on postoperative fentanyl consumption in Korean gynecologic patients.
abstract: OBJECTIVE
  Fentanyl, a μ-opioid receptor agonist, is a substrate of P-glycoprotein. Its metabolism is catalyzed by CYP3A4 and CYP3A5. The aim of this study was to investigate the association between postoperative fentanyl consumption and genetic polymorphisms of μ-opioid receptor (OPRM1), ABCB1 (gene encoding P-glycoprotein), CYP3A4 and CYP3A5 in Korean patients.
  
  
  METHODS
  196 female patients scheduled to undergo total abdominal hysterectomy or laparoscopic assisted vaginal hysterectomy under general anesthesia were enrolled in this study. Intravenous patient-controlled analgesia with fentanyl was provided postoperatively. Cumulative fentanyl consumption was measured during the first 48 hours postoperatively. The severity of pain at rest was assessed with the visual analogue scale. OPRM1 118A>G, ABCB1 2677G>A/T, ABCB1 3435C>T, CYP3A4*18 and CYP3A5*3 variant alleles were genotyped. The effects of genetic and non-genetic factors on fentanyl requirements were evaluated with multiple linear regression analysis.
  
  
  RESULTS
  The 24-hour cumulative fentanyl doses were significantly associated with pain core, weight and type of surgery (p < 0.05). The 48-hour cumulative fentanyl doses were significantly associated with pain score, type of surgery and history of PONV or motion sickness (p < 0.05). Genetic polymorphisms were not associated with fentanyl requirements.
  
  
  CONCLUSIONS
  In Korean gynecologic patients, no association was found between genetic factors and postoperative fentanyl consumption.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Inje University Sanggye Paik Hospital, Seoul, Republic of Korea.
authors.forename: Kye-Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Ho-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Se Hun
authors.initials: SH
authors.lastname: Lim
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Cheong
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Choi
authors.forename: Hyun
authors.initials: H
authors.lastname: Kang
authors.forename: Hey-Ran
authors.initials: HR
authors.lastname: Choi
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeon
authors.forename: Jun Heum
authors.initials: JH
authors.lastname: Yon
authors.forename: Minkyung
authors.initials: M
authors.lastname: Oh
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D044466:Asian People / Q000235:genetics; D016009:Chi-Square Distribution; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects*; D006801:Humans; D007045:Hysterectomy, Vaginal / Q000009:adverse effects; D010535:Laparoscopy / Q000009:adverse effects; D016014:Linear Models; D016015:Logistic Models; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011182:Postoperative Care; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D056910:Republic of Korea; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D005283:Fentanyl