title: Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype.
abstract: OBJECTIVE
  Determine whether SNPs of OPRM1 118A>G (asn(40)asp), COMT 472G>A (val(158)met) and ARRB2 8622C>T are associated with morphine rescue in newborns on mechanical ventilation.
  
  
  METHODS
  This is a pharmacogenetic analysis of a randomized controlled trial in (pre)term newborns (n = 64) at a level III Neonatal Intensive Care Unit (NICU) who received placebo infusion and for whom need and dose for rescue morphine was documented.
  
  
  RESULTS
  For OPRM1 and COMT separately, the expected risk for rescue morphine or morphine dose was not significantly increased. However, the combined OPRM1/COMT 'high-risk' genotype lead to a significant association with the need for rescue (OR: 5.12; 95% CI: 1.12-23.3; p = 0.035). No association was found between OPRM1/COMT 'high-risk' genotype and total morphine dose administered.
  
  
  CONCLUSIONS
  Combined OPRM1 118A>G and COMT 472G>A genotype might serve as a predictor for the need of rescue morphine in premature and term newborns on mechanical ventilation.
authors.affiliation: Department of Clinical Chemistry, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
authors.forename: Maja
authors.initials: M
authors.lastname: Matic
authors.forename: Sinno H P
authors.initials: SH
authors.lastname: Simons
authors.forename: Richard A
authors.initials: RA
authors.lastname: van Lingen
authors.forename: Joost
authors.initials: J
authors.lastname: van Rosmalen
authors.forename: Laure
authors.initials: L
authors.lastname: Elens
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
mesh_terms: D000698:Analgesia / Q000009:adverse effects; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D015931:Intensive Care, Neonatal; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; OPRM1; morphine; newborns; pain; pediatric; pharmacogenetics; ventilation