title: The effect of OPRM1 and COMT genotypes on the analgesic response to intravenous fentanyl labor analgesia.
abstract: BACKGROUND
  IV fentanyl is used as a labor analgesic; however, few studies have reported the effects of IV fentanyl for early labor analgesia. We evaluated the analgesic response to IV fentanyl according to the combined effect of the single-nucleotide polymorphisms rs1799971 (c.118A/G, p. 40Asn/Asp) of the µ-opioid receptor gene (OPRM1) and rs4680 (c.472G/A, p.158Val/Met) of the catechol-O-methyltransferase (COMT) gene in women requesting labor analgesia.
  
  
  METHODS
  Labor analgesia was initiated with IV fentanyl 1.5 μg/kg. The primary outcome was analgesic success, defined as Numerical Verbal Pain Scale score≤10/100 15 minutes after the dose of fentanyl. Analgesic and side effect outcomes were compared according to OPRM1 and COMT genotypes.
  
  
  RESULTS
  One hundred six women were enrolled and received IV fentanyl. IV analgesic success was 6% in women with the combination Asn/Asn-Met/Met (n=17) versus 20% in all other women combined (not Asn/Asn-Met/Met; P=0.30; difference=14%; 95% confidence interval [CI], -10% to 26%). IV analgesic success was 20% in women 118A/A (Asn/Asn) versus 21% for A/G and G/G of OPRM1 (P=0.82; difference=2%; 95% CI, -17% to 19%), and 10% in women 472A (Met/Met) versus 22% for A/G (Met/Val) and G/G (Val/Val) of COMT (P=0.24; difference=12%; 95% CI, -6% to 26%). Met/Met158 (n=31) versus Met/Val or Val/Val of COMT was associated with a smaller decrease in Numerical Verbal Pain Scale (24±18 vs 37±23; P=0.005; mean difference=-13; 99% CI, -25 to -1).
  
  
  CONCLUSIONS
  This study was underpowered to draw firm conclusions on the influence of OPRM1 and COMT genotypes on labor analgesia with IV fentanyl. Further larger studies are needed to evaluate whether genotyping COMT alone or in combination with OPRM1 may have potentially useful clinical implications, such as not offering IV fentanyl in early labor to women who will most likely not benefit from it.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Washington, Medical Center, 1959 NE Pacific Street, Suite BB 1415B, Seattle, WA 98195, USA. rulandau@u.washington.edu
authors.forename: Ruth
authors.initials: R
authors.lastname: Landau
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Liu
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
authors.forename: Brendan
authors.initials: B
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D016362:Analgesia, Obstetrical; D000701:Analgesics, Opioid; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005283:Fentanyl; D005838:Genotype; D006801:Humans; D010147:Pain Measurement; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; 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; D004247:DNA; D002394:Catechol O-Methyltransferase; D005283:Fentanyl