ABCC3 genetic variants are associated with postoperative morphine-induced respiratory depression and morphine pharmacokinetics in children

The Pharmacogenomics Journal
Vidya ChidambaranSenthilkumar Sadhasivam

Abstract

Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux) affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1.28-4.37, P=0.0061) and 3.7 (95% CI 1.47-9.09, P=0.0050) times increase in odds of prolonged RD, respectively. These clinical associations were supported by increased formation clearance of morphine glucuronides in children with rs4148412 AA and rs4973665 CC genotypes in this cohort, as well as an independent spine surgical cohort of 67 adolescents. This is the first study to report association of ABCC3 variants with opioid-related RD, and morphine metabolite formation (in two independent surgical cohorts).

Associated Clinical Trials

Jun 9, 2010·Senthilkumar Sadhasivam, MD, MPH

References

Jan 1, 1997·Acta Anaesthesiologica Scandinavica·L L Christrup
Mar 30, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J KönigD Keppler
Jun 5, 2002·Annual Review of Biochemistry·P Borst, R Oude Elferink
Oct 25, 2003·Oncogene·Gary D Kruh, Martin G Belinsky
Dec 10, 2003·Clinical Pharmacology and Therapeutics·Evan D KharaschPam Sheffels
May 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Noam ZelcerPiet Borst
Jul 19, 2005·Computer Methods and Programs in Biomedicine·Lars LindbomNiclas Jonsson
Oct 20, 2006·Clinical Pharmacokinetics·Jörn LötschGerd Geisslinger
Mar 21, 2007·Archives of Otolaryngology--head & Neck Surgery·Ronald D ChervinKenneth E Guire
Feb 12, 2009·Therapeutics and Clinical Risk Management·Karamarie FechoEdward A Norfleet
Jun 11, 2009·Pharmacogenetics and Genomics·Caroline F ThornRuss B Altman
Sep 11, 2009·Nature·Axel ViselLen A Pennacchio
Oct 27, 2009·Current Opinion in Genetics & Development·Nathaniel D Heintzman, Bing Ren
Jan 9, 2010·Therapeutics and Clinical Risk Management·Karamarie FechoFrank J Overdyk
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Menno P CreyghtonRudolf Jaenisch
Jun 21, 2012·Anesthesiology·Martin S AngstJ David Clark
Sep 8, 2012·Genome Research·Marc A SchaubMichael Snyder
Sep 8, 2012·Genome Research·Alan P BoyleMichael Snyder
Jul 19, 2013·Pharmacogenomics·Tsuyoshi FukudaSenthilkumar Sadhasivam
Oct 19, 2013·Science·Graham McVickerJonathan K Pritchard
Aug 27, 2014·Pharmacogenomics·Raja VenkatasubramanianSenthilkumar Sadhasivam
Oct 15, 2014·The Pharmacogenomics Journal·S SadhasivamJ McAuliffe

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Citations

Oct 26, 2013·European Journal of Pharmacology·Howard S Smith, Andras Laufer
Jul 12, 2018·Current Opinion in Anaesthesiology·Vinko PaladaEija Kalso
May 16, 2018·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Christiane Vleminckx
Jun 30, 2019·Pharmacogenomics·Sanjida AhmedJunaid A Bhatti
Oct 14, 2020·Expert Opinion on Drug Metabolism & Toxicology·Matthijs W van HoogdalemTomoyuki Mizuno
Jan 19, 2021·Expert Opinion on Drug Metabolism & Toxicology·Henrike Bruckmueller, Ingolf Cascorbi
Dec 6, 2019·Peptides·Richard J Bodnar
Nov 18, 2020·Chemical Reviews·Tim KrollLutz Schmitt

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Methods Mentioned

BETA
genotyping

Clinical Trials Mentioned

NCT01140724
NCT01839461

Software Mentioned

Toolkit
PLINK
NONMEM
Illumina Genome Studio
Statistical Analysis Software ( SAS )
Quanto
R
PsN
RegulomeDB

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