title: A non-synonymous single nucleotide polymorphism in an OPRM1 splice variant is associated with fentanyl-induced emesis in women undergoing minor gynaecological surgery.
abstract: BACKGROUND
  Fentanyl-induced emesis (FIE) is a distressing adverse effect in the postoperative setting. The genetic basis of FIE remains largely unknown, therefore, we examined whether it was associated with specific genetic variants of OPRM1, the gene encoding the main receptor target of fentanyl.
  
  
  METHODS
  In this prospective case-control study, 193 women undergoing gynaecological surgery under a standardized anaesthetic with a low emetogenic risk were enrolled. Inclusion and exclusion criteria were designed to select extreme phenotypes as well as to ensure that most major confounders for FIE were either excluded or present in all patients. To control for unforeseen intra- and postoperative confounders for FIE, only 161 patients were further analysed, out of which 10 were categorized as having FIE, defined by the presence of at least one of three symptoms: nausea, vomiting or retching that was likely to be fentanyl-related. To identify SNPs relevant to FIE in our population, DNA from 40 controls and 10 cases was sequenced at the following OPRM1 regions: 3 kbp of the promoter, main and alternative exons as well as 2 kbp of the 3' downstream region. The genotype of the significant SNP was further determined in the remaining 111 controls.
  
  
  RESULTS
  The incidence of FIE was 6.2%. Initial sequencing of 10 cases and 40 controls identified 25 SNPs. Only rs540825, a non-synonymous SNP in the splice variant, MOR1X, showed a significant association with FIE post-Bonferroni correction. This SNP was further examined in the remaining 111 controls which confirmed its significant association with FIE (p = 0.019 post-Bonferroni, OR: 5.6, 95% CI: 1.42-21.91).
  
  
  CONCLUSIONS
  This is the first report of an association between the occurrence of FIE in Chinese women undergoing gynaecological surgery and an OPRM1 splice variant SNP, rs540825.
authors.affiliation: Liver Cancer Functional Genomics Laboratory, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Grace Su Yin
authors.initials: GS
authors.lastname: Pang
authors.forename: Farida
authors.initials: F
authors.lastname: Ithnin
authors.forename: Yin Yee
authors.initials: YY
authors.lastname: Wong
authors.forename: Jing Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lim
authors.forename: Alex Tiong Heng
authors.initials: AT
authors.lastname: Sia
authors.forename: Caroline Guat Lay
authors.initials: CG
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D014839:Vomiting / Q000139:chemically induced* / Q000235:genetics*; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D005283:Fentanyl