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Human Genetic Variability Contributes to Postoperative Morphine Consumption.

Publication ,  Journal Article
De Gregori, M; Diatchenko, L; Ingelmo, PM; Napolioni, V; Klepstad, P; Belfer, I; Molinaro, V; Garbin, G; Ranzani, GN; Alberio, G; Normanno, M ...
Published in: J Pain
May 2016

UNLABELLED: High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor μ 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. PERSPECTIVE: This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. REGISTERED ON CLINICALTRIALS.GOV: NCT01233752.

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Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

May 2016

Volume

17

Issue

5

Start / End Page

628 / 636

Location

United States

Related Subject Headings

  • Young Adult
  • Time Factors
  • Receptors, Opioid, mu
  • Polymorphism, Single Nucleotide
  • Pharmacogenomic Testing
  • Pain, Postoperative
  • Outcome Assessment, Health Care
  • Morphine
  • Middle Aged
  • Male
 

Citation

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Chicago
ICMJE
MLA
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De Gregori, M., Diatchenko, L., Ingelmo, P. M., Napolioni, V., Klepstad, P., Belfer, I., … Allegri, M. (2016). Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain, 17(5), 628–636. https://doi.org/10.1016/j.jpain.2016.02.003
De Gregori, Manuela, Luda Diatchenko, Pablo M. Ingelmo, Valerio Napolioni, Pal Klepstad, Inna Belfer, Valeria Molinaro, et al. “Human Genetic Variability Contributes to Postoperative Morphine Consumption.J Pain 17, no. 5 (May 2016): 628–36. https://doi.org/10.1016/j.jpain.2016.02.003.
De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I, et al. Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain. 2016 May;17(5):628–36.
De Gregori, Manuela, et al. “Human Genetic Variability Contributes to Postoperative Morphine Consumption.J Pain, vol. 17, no. 5, May 2016, pp. 628–36. Pubmed, doi:10.1016/j.jpain.2016.02.003.
De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I, Molinaro V, Garbin G, Ranzani GN, Alberio G, Normanno M, Lovisari F, Somaini M, Govoni S, Mura E, Bugada D, Niebel T, Zorzetto M, De Gregori S, Molinaro M, Fanelli G, Allegri M. Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain. 2016 May;17(5):628–636.
Journal cover image

Published In

J Pain

DOI

EISSN

1528-8447

Publication Date

May 2016

Volume

17

Issue

5

Start / End Page

628 / 636

Location

United States

Related Subject Headings

  • Young Adult
  • Time Factors
  • Receptors, Opioid, mu
  • Polymorphism, Single Nucleotide
  • Pharmacogenomic Testing
  • Pain, Postoperative
  • Outcome Assessment, Health Care
  • Morphine
  • Middle Aged
  • Male