title: Opioid-induced respiratory depression: ABCB1 transporter pharmacogenetics.
abstract: Opioid-related respiratory depression (RD) is a serious clinical problem as it causes multiple deaths and anoxic brain injuries. Morphine is subject to efflux via P-glycoprotein transporter encoded by ABCB1, also known as MDR1. ABCB1 polymorphisms may affect blood-brain barrier transport of morphine and therefore individual response to its central analgesic and adverse effects. This study aimed to determine specific associations between common ABCB1 genetic variants and clinically important outcomes including RD and RD resulting in prolonged stay in hospital with intravenous morphine in a homogenous pediatric surgical pain population of 263 children undergoing tonsillectomy. Children with GG and GA genotypes of ABCB1 polymorphism rs9282564 had higher risks of RD resulting in prolonged hospital stays; adding one copy of the minor allele (G) increased the odds of prolonged hospital stay due to postoperative RD by 4.7-fold (95% confidence interval: 2.1-10.8, P=0.0002).
authors.affiliation: 1] Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sadhasivam
authors.affiliation: 1] Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: V
authors.identifier: 0000000179131932
authors.initials: V
authors.lastname: Chidambaran
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Division of Bioinformatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Meller
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: H
authors.initials: H
authors.lastname: Esslinger
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Martin
authors.affiliation: 1] Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: McAuliffe
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000483:Alleles; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007902:Length of Stay; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D010597:Pharmacogenetics / Q000379:methods; D011446:Prospective Studies; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000235:genetics*; D012306:Risk
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000701:Analgesics, Opioid; D009020:Morphine