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.

Fatty Acid Amide Hydrolase–morphine Interaction Influences Ventilatory Response to Hypercapnia and Postoperative Opioid Outcomes in Children

“…Twin studies have revealed significant heritability (30%) for RD from opioids [62]; contributing nongenetic risk factors like female sex and medical comorbidities have been described [63][64][65]. Our study strengthens the evidence for FAAH associations with morphine outcomes in children, adds to the genetic risk factors reported previously -OPRM1 [66] and ABCB1 [67] and expands the knowledge base toward identifying genetic risk signatures for RD in children [68]. FAAH inhibitors have been explored for treatment of pain and nausea [69,70]; our findings spur further investigation of these agents to alter risk of opioid RD.…”

Morphine versus methylprednisolone or aminophylline for relieving dyspnea in patients with advanced cancer in China: a retrospective study

“…However, the use of morphine is at risk of addiction and respiratory depression (Chidambaran et al 2015). Many physicians and patients are reluctant to use morphine for fear of respiratory depression and the lack of comprehensive understanding about morphine.…”

Molecular Basis of Opioid Action: From Structures to New Leads

“…This mutation leads to decreased cell surface expression and overall receptor stability combined with more subtle effects on the binding affinity of opioid peptides and small molecules (69,70). Increasing evidence suggests that this variant may alter pain threshold levels, sensitivity to clinically used opioids, and risk of opioidinduced respiratory depression (71)(72)(73). At a structural level, the direct consequence of this variant remains unknown owing to truncations in the presumably flexible amino terminus required for crystallography.…”