Advanced

Genetic Predisposition to Poor Opioid Response in Preterm Infants : Impact of KCNJ6 and COMT Polymorphisms on Pain Relief after Endotracheal Intubation

Elens, Laure; Norman, Elisabeth LU ; Matic, Maja; Rane, Anders; Fellman, Vineta LU and Van Schaik, Ron H N (2016) In Therapeutic Drug Monitoring 38(4). p.525-533
Abstract

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, Val 158 Met) 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... (More)

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, Val 158 Met) 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 158 Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
catechol-O-methyl transferase, opioids, pain, pharmacogenetics, potassium inwardly rectifying channel subfamily J member 6
in
Therapeutic Drug Monitoring
volume
38
issue
4
pages
9 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:84961901852
  • wos:000381427700014
ISSN
0163-4356
DOI
10.1097/FTD.0000000000000301
language
English
LU publication?
yes
id
d69c0fb8-2e15-49ec-94e3-d3322e4da44a
date added to LUP
2016-12-30 12:37:15
date last changed
2017-11-05 05:11:51
@article{d69c0fb8-2e15-49ec-94e3-d3322e4da44a,
  abstract     = {<p>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&gt;A (rs6517442, c.-1787G&gt;A) and the catecholamine-O-methyltransferase (COMT) c.472G&gt;A (rs4680, Val 158 Met) 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 158 Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.</p>},
  author       = {Elens, Laure and Norman, Elisabeth and Matic, Maja and Rane, Anders and Fellman, Vineta and Van Schaik, Ron H N},
  issn         = {0163-4356},
  keyword      = {catechol-O-methyl transferase,opioids,pain,pharmacogenetics,potassium inwardly rectifying channel subfamily J member 6},
  language     = {eng},
  month        = {08},
  number       = {4},
  pages        = {525--533},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Therapeutic Drug Monitoring},
  title        = {Genetic Predisposition to Poor Opioid Response in Preterm Infants : Impact of KCNJ6 and COMT Polymorphisms on Pain Relief after Endotracheal Intubation},
  url          = {http://dx.doi.org/10.1097/FTD.0000000000000301},
  volume       = {38},
  year         = {2016},
}