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Pharmacogenomics J. 2019 Feb 14. doi: 10.1038/s41397-019-0074-4. [Epub ahead of print]

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

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Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
New Jersey Institute of Technology, Newark, NJ, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.


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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