title: Influence of CYP3A5*3 polymorphism and interaction between CYP3A5*3 and CYP3A4*1G polymorphisms on post-operative fentanyl analgesia in Chinese patients undergoing gynaecological surgery.
abstract: OBJECTIVE
  Fentanyl is metabolised by cytochrome P450 (CYP) 3A4 and CYP3A5. Our previous work demonstrated that the CYP3A4*1G polymorphism significantly affects the post-operative fentanyl analgesic effect in Chinese women undergoing gynaecological surgery. However, whether CYP3A5*3, a frequent single nucleotide polymorphism of CYP3A5 in Chinese people, affects the post-operative analgesic effect of fentanyl is unclear. In this study, we assessed the influence of the CYP3A5*3 polymorphism and the interaction of the CYP3A5*3 and CYP3A4*1G polymorphisms on post-operative fentanyl analgesia in Chinese women undergoing gynaecological surgery.
  
  
  METHODS
  We enrolled 203 women scheduled for abdominal total hysterectomy or myomectomy under general anaesthesia. Intravenous fentanyl patient-controlled analgesia was provided post-operatively for adequate analgesia. Pain scores and fentanyl consumption were recorded 24 h post-operatively. Midazolam was used as a probe drug, and CYP3A activity was measured by plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg kg-1 midazolam. Blood samples were genotyped for the CYP3A5*3 polymorphism.
  
  
  RESULTS
  The frequency of the CYP3A5*3 allele was 72.4% in 203 patients. CYP3A activity did not differ among CYP3A5*3 genotypes. Fentanyl consumption 24 h post-operatively was lower with CYP3A5*1/*3 and CYP3A5*3/*3 polymorphisms than with CYP3A5*1/*1, but the differences were not statistically significant. However, combined with CYP3A4*1G polymorphism, post-operative fentanyl consumption at 24 h was significantly lower for the CYP3A5*1/*3 or CYP3A5*3/*3 group than the CYP3A5*1/*1 group.
  
  
  CONCLUSIONS
  CYP3A5*3 is not the main genetic factor contributing to interindividual variation in the post-operative analgesic effect of fentanyl in Chinese women undergoing gynaecological surgery; an interaction between CYP3A5*3 and CYP3A4*1G polymorphisms can significantly influence the post-operative effect.
authors.affiliation: Department of Anaesthesia, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yuan
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Zhang
authors.forename: Yan-Zi
authors.initials: YZ
authors.lastname: Chang
authors.forename: Zhong-Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Zhi-Song
authors.initials: ZS
authors.lastname: Li
mesh_terms: D000328:Adult; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000378:metabolism; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects*; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D013997:Time Factors; D063186:Uterine Myomectomy / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D005283:Fentanyl