Genetic predisposition to poor opioid response in preterm infants: Impact of KCNJ6 and COMT polymorphisms on pain relief after endotracheal intubation.
(2016) Therapeutic Drug Monitoring — Vol. 38, n° 4, p. 525-533 (2016)
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- (en) BACKGROUND: Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, ValMet) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n = 17) or morphine (n = 17). METHODS: Pain was scored with Astrid Lindgren and Lund Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes. RESULTS: Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank = 7.5, P = 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank = 14.4, P = 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy. CONCLUSION: We conclude that the KCNJ6 -1250A and COMT Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.
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Elens, L., Elisabeth, N., Maja, M., Rane, A., Fellman, V., & van Schaik, R. H. (2016). Genetic predisposition to poor opioid response in preterm infants: Impact of KCNJ6 and COMT polymorphisms on pain relief after endotracheal intubation. Therapeutic Drug Monitoring, 38(4), 525-533. https://doi.org/10.1097/FTD.0000000000000301 (Original work published 2016)