Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents

The mu 1 opioid receptor (OPRM1) genetic variant A118G results in decreased mu-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.