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Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits

The Pharmacogenomics Journal volume 19, pages 570–581 (2019)Cite this article

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Abstract

Acute pain and opioid analgesia demonstrate inter-individual variability and polygenic influence. In 241 children of African American and 277 of European Caucasian ancestry, we sought to replicate select candidate gene associations with morphine dose and postoperative pain and then to estimate dose prediction limits. Twenty-seven single-nucleotide polymorphisms (SNPs) from nine genes (ABCB1, ARRB2, COMT, DRD2, KCNJ6, MC1R, OPRD1, OPRM1, and UGT2B7) met selection criteria and were analyzed along with TAOK3. Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = −9.30, 95% CI: −17.25 to −1.35, p = 0.02) and OPRM1 rs1799971 (G allele, β = 23.19, 95% CI: 3.27–43.11, p = 0.02); KCNJ6 rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI: 1.17–3.71, p = 0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR: 0.69, 95% CI: 0.48–0.99, p = 0.046). With age, body mass index, and physical status as covariates, simple top SNP candidate gene models could explain theoretical maximums of 24.2% (European Caucasian) and 14.6% (African American) of morphine dose variances.

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Acknowledgements

Funding for this work was provided by the Department of Anesthesiology and Critical Care Medicine through Children’s Anesthesia Associates, Ltd. (Philadelphia, PA, USA) and by The Children’s Hospital of Philadelphia (Philadelphia, PA, USA) through a grant from its Institutional Development Fund to The Center for Applied Genomics. Dr. Hakonarson is a recipient of funding from the National Institutes of Health, NHGRI eMERGE grant U01HG006830. A portion of this work was presented by Dr. Li at the October 2018 annual meeting of the American Society of Human Genetics in San Diego, CA, USA.

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Authors and Affiliations

  1. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China

    Jin Li

  2. Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jin Li & Hakon Hakonarson

  3. New Jersey Institute of Technology, Newark, NJ, USA

    Zhi Wei & Jie Zhang

  4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Hakon Hakonarson & Scott D. Cook-Sather

  5. Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Scott D. Cook-Sather

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  1. Jin Li
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  2. Zhi Wei
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  3. Jie Zhang
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  4. Hakon Hakonarson
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Correspondence to Scott D. Cook-Sather.

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Li, J., Wei, Z., Zhang, J. et al. Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits. Pharmacogenomics J 19, 570–581 (2019). https://doi.org/10.1038/s41397-019-0074-4

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  • DOI: https://doi.org/10.1038/s41397-019-0074-4

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