title: Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents.
abstract: The μ1 opioid receptor (OPRM1) genetic variant A118G results in decreased μ-receptor binding potential in the brain and increases morphine requirement. We hypothesized that OPRM1 A118G polymorphism will affect morphine-induced respiratory depression (MIRD) risk in children receiving morphine. A prospective genotype-blinded study was conducted in 88 healthy adolescents (11-18 years; 67% female, 85% Caucasian) who underwent spine fusion for scoliosis. They were followed for 48 h postoperatively for MIRD, pain scores, morphine consumption and use of analgesic adjuvants. Patients were genotyped for OPRM1 A118G variant-76% were wild type (AA) and 24% heterozygous/homozygous for variant (AG/GG). Multivariable logistic regression showed that the risk of MIRD in patients with AA genotype was significantly higher (odds ratio 5.6, 95% CI: 1.4-37.2, P=0.030). Presence of G allele was associated with higher pain scores (effect size 0.73, P=0.045). This novel association is an important step toward predicting MIRD susceptibility and personalizing morphine use.
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.initials: V
authors.lastname: Chidambaran
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: Mavi
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: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: V
authors.initials: V
authors.lastname: Pilipenko
authors.affiliation: 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: 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 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
mesh_terms: D000293:Adolescent; D000483:Alleles; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D012600:Scoliosis / Q000601:surgery; D013131:Spine / Q000601:surgery*
chemical_list: D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine