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: V Chidambaran, J Mavi, H Esslinger, V Pilipenko, L J Martin, K Zhang, S Sadhasivam
• Journal: The pharmacogenomics journal (Pharmacogenomics J) Vol. 15 Issue 3 Pg. 255-62 (Jun 2015) ISSN: 1473-1150 [Electronic] United States
• PMID: 25266679 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• OPRM1 protein, human
• Receptors, Opioid, mu
• Morphine

Topics

• Adolescent
• Alleles
• Analgesics, Opioid (administration & dosage, adverse effects)
• Child
• Female
• Genotype
• Homozygote
• Humans
• Male
• Morphine (administration & dosage, adverse effects)
• Polymorphism, Single Nucleotide (genetics)
• Prospective Studies
• Receptors, Opioid, mu (genetics, metabolism)
• Respiratory Insufficiency (chemically induced, genetics, metabolism)
• Risk
• Scoliosis (surgery)
• Spine (surgery)