Aim: Determine whether SNPs of OPRM1 118A>G (asn<sup>40</sup>asp), COMT 472G>A (val<sup>158</sup>met) and ARRB2 8622C>T are associated with morphine rescue in newborns on mechanical ventilation. Materials & methods: This is a pharmacogenetic analysis of a randomized controlled trial in (pre)term newborns (n = 64) at a level III Neonatal Intensive Care Unit (NICU) who received placebo infusion and for whom need and dose for rescue morphine was documented. Results: For OPRM1 and COMT separately, the expected risk for rescue morphine or morphine dose was not significantly increased. However, the combined OPRM1/COMT 'high-risk' genotype lead to a significant association with the need for rescue (OR: 5.12; 95% CI: 1.12-23.3; p = 0.035). No association was found between OPRM1/COMT 'high-risk' genotype and total morphine dose administered. Conclusion: Combined OPRM1 118A>G and COMT 472G>A genotype might serve as a predictor for the need of rescue morphine in premature and term newborns on mechanical ventilation.

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Keywords COMT, morphine, newborns, OPRM1, pain, pediatric, pharmacogenetics, ventilation
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Journal Pharmacogenomics
Matić, M, Simons, S.H, Lingen, R.A, van Rosmalen, J.M, Elens, L, de Wildt, S.N, … van Schaik, R.H.N. (2014). Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics, 15(10), 1287–1295. doi:10.2217/pgs.14.100