title: Fatty acid amide hydrolase-morphine interaction influences ventilatory response to hypercapnia and postoperative opioid outcomes in children.
abstract: OBJECTIVE
  Fatty acid amide hydrolase (FAAH) degrades anandamide, an endogenous cannabinoid. We hypothesized that FAAH variants will predict risk of morphine-related adverse outcomes due to opioid-endocannabinoid interactions.
  
  
  METHODS
  In 101 postsurgical adolescents receiving morphine analgesia, we prospectively studied ventilatory response to 5% CO2(HCVR), respiratory depression (RD) and vomiting. Blood was collected for genotyping and morphine pharmacokinetics.
  
  
  RESULTS
  We found significant FAAH-morphine interaction for missense (rs324420) and several regulatory variants, with HCVR (p < 0.0001) and vomiting (p = 0.0339). HCVR was more depressed in patients who developed RD compared with those who did not (p = 0.0034), thus FAAH-HCVR association predicts risk of impending RD from morphine use.
  
  
  CONCLUSIONS
  FAAH genotypes predict risk for morphine-related adverse outcomes.
authors.affiliation: Department of Anesthesia, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Chidambaran
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pilipenko
authors.affiliation: Department of Anesthesia, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Kristie
authors.initials: K
authors.lastname: Spruance
authors.affiliation: Department of Anesthesia, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Anesthesia, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.|Division of Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Niu
authors.affiliation: Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.|Division of Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Division of Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kaufman
authors.affiliation: Division of Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
authors.affiliation: Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.|Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Martin
authors.affiliation: Department of Anesthesia, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sadhasivam
mesh_terms: D000293:Adolescent; D000581:Amidohydrolases / Q000097:blood* / Q000235:genetics*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000097:blood; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000097:blood* / Q000139:chemically induced / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000097:blood*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011183:Postoperative Complications / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D011446:Prospective Studies; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000701:Analgesics, Opioid; D009020:Morphine; D000099252:Fatty Acid Amide Hydrolases
keywords: FAAH; fatty acid amide hydrolase; hypercapnic ventilatory response; morphine; opioid–cannabinoid interactions; postoperative; respiratory depression