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)
- author
- Elens, Laure
; Norman, Elisabeth
LU
; Matic, Maja
; Rane, Anders
; Fellman, Vineta
LU
and Van Schaik, Ron H N
- organization
- publishing date
- 2016-08-01
- 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
-
- pmid:27027462
- wos:000381427700014
- scopus:84961901852
- 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
- 2024-04-05 14:00:28
@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>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.</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}},
keywords = {{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}},
doi = {{10.1097/FTD.0000000000000301}},
volume = {{38}},
year = {{2016}},
}