Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption

Keith A Candiotti, Zongqi Yang, Richard Morris, Jinfeng Yang, Nicolas A. Crescimone, Greys C. Sanchez, Vincent Bird, Raymond Leveillee, Yiliam Rodriguez, Huanliang Liu, Yu Zhang, John R. Bethea, Melvin C. Gitlin

Research output: Contribution to journalArticle

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Abstract

Background: The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period. Methods: Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured. Results: Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43% (95% CI, 38-48%) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations. Conclusions: The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele.

Original languageEnglish
Pages (from-to)1162-1168
Number of pages7
JournalAnesthesiology
Volume114
Issue number5
DOIs
StatePublished - May 1 2011

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Interleukin 1 Receptor Antagonist Protein
Interleukin-1 Receptors
Opioid Analgesics
Serum
Genes
Interleukin-1
Minisatellite Repeats
Genotype
Homozygote
Postoperative Period
Introns
Alleles
Narcotic Antagonists
Multigene Family
Nephrectomy
Base Pairing
Pain
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption. / Candiotti, Keith A; Yang, Zongqi; Morris, Richard; Yang, Jinfeng; Crescimone, Nicolas A.; Sanchez, Greys C.; Bird, Vincent; Leveillee, Raymond; Rodriguez, Yiliam; Liu, Huanliang; Zhang, Yu; Bethea, John R.; Gitlin, Melvin C.

In: Anesthesiology, Vol. 114, No. 5, 01.05.2011, p. 1162-1168.

Research output: Contribution to journalArticle

Candiotti, Keith A ; Yang, Zongqi ; Morris, Richard ; Yang, Jinfeng ; Crescimone, Nicolas A. ; Sanchez, Greys C. ; Bird, Vincent ; Leveillee, Raymond ; Rodriguez, Yiliam ; Liu, Huanliang ; Zhang, Yu ; Bethea, John R. ; Gitlin, Melvin C. / Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption. In: Anesthesiology. 2011 ; Vol. 114, No. 5. pp. 1162-1168.
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abstract = "Background: The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period. Methods: Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured. Results: Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43{\%} (95{\%} CI, 38-48{\%}) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations. Conclusions: The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele.",
author = "Candiotti, {Keith A} and Zongqi Yang and Richard Morris and Jinfeng Yang and Crescimone, {Nicolas A.} and Sanchez, {Greys C.} and Vincent Bird and Raymond Leveillee and Yiliam Rodriguez and Huanliang Liu and Yu Zhang and Bethea, {John R.} and Gitlin, {Melvin C.}",
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T1 - Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption

AU - Candiotti, Keith A

AU - Yang, Zongqi

AU - Morris, Richard

AU - Yang, Jinfeng

AU - Crescimone, Nicolas A.

AU - Sanchez, Greys C.

AU - Bird, Vincent

AU - Leveillee, Raymond

AU - Rodriguez, Yiliam

AU - Liu, Huanliang

AU - Zhang, Yu

AU - Bethea, John R.

AU - Gitlin, Melvin C.

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Background: The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period. Methods: Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured. Results: Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43% (95% CI, 38-48%) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations. Conclusions: The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele.

AB - Background: The interleukin-1 receptor antagonist (IL-1Ra) is the principal determinant of IL-1β bioactivity within the IL-1 gene cluster, regulating IL-1α and IL-1β release. This study was designed to determine whether polymorphisms of the IL-1Ra gene (IL1RN) produce clinically measurable differences in serum IL-1Ra concentrations and opioid consumption in the postoperative period. Methods: Opioid consumption and pain scores were evaluated in 96 patients undergoing a nephrectomy. DNA was extracted from all patients, and the genotypes of IL1RN were determined by polymerase chain reaction amplification of the variable number of tandem repeats of 86 base pairs in intron 2 of IL1RN. The concentrations of serum IL-1Ra concentrations at baseline and at 24 h postoperatively in 58 subjects were measured. Results: Differences in opioid consumption among the three genotype groups (IL1RN*1 homozygotes and *2 and *3 carriers) were statistically significant in the first and second 12-h postoperative periods (P = 0.010). The IL1RN*2 carrier group consumed 43% (95% CI, 38-48%) less opioids in the first 24 h after surgery than the IL1RN*1 homozygote group (P = 0.003). Differences in the serum IL-1Ra concentration among the three genotype groups were statistically significant at 24 h postoperatively (P = 0.003), with IL1RN*2 carriers having the highest serum IL-1Ra concentrations. Conclusions: The variable number of tandem repeats in intron 2 of IL1RN may contribute to interindividual variations in opioid consumption in the first 24 h after surgery. Patients homozygous for the IL1RN*1 allele have lower concentrations of IL-1Ra and require higher doses of opioids postoperatively than patients carrying at least one IL1RN*2 allele.

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DO - 10.1097/ALN.0b013e318216e9cb

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