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

The Pharmacogenomics Journal volume 15, pages 255–262 (2015)Cite this article

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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.

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Acknowledgements

The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant 8 UL1 TR000077 through the T1 Junior Faculty Award and Clinical Research Feasibility Funds (PI: Chidambaran). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. It was also supported by the APSF / ASA Safety Scientist Career Development Award by the Anesthesia Patient Safety Foundation (PI: Chidambaran). We acknowledge the contributions of the Clinical Analytic support team at Cincinnati Children’s Hospital for their assistance with medical record data retrieval.

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Authors and Affiliations

  1. Department of Anesthesia, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    V Chidambaran, J Mavi, H Esslinger & S Sadhasivam

  2. Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    V Chidambaran, J Mavi & S Sadhasivam

  3. Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    V Pilipenko, L J Martin & K Zhang

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  1. V Chidambaran
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Correspondence to V Chidambaran.

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Chidambaran, V., Mavi, J., Esslinger, H. et al. Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents. Pharmacogenomics J 15, 255–262 (2015). https://doi.org/10.1038/tpj.2014.59

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