title: Polymorphism in the interleukin-1 receptor antagonist gene is associated with serum interleukin-1 receptor antagonist concentrations and postoperative opioid consumption.
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.
authors: Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami, Miller School of Medicine, Miami, Florida 33101, USA. kcandiotti@miami.edu
authors: Keith A
authors: KA
authors: Candiotti
authors: Zongqi
authors: Z
authors: Yang
authors: Richard
authors: R
authors: Morris
authors: Jinfeng
authors: J
authors: Yang
authors: Nicolas A
authors: NA
authors: Crescimone
authors: Greys C
authors: GC
authors: Sanchez
authors: Vincent
authors: V
authors: Bird
authors: Raymond
authors: R
authors: Leveillee
authors: Yiliam
authors: Y
authors: Rodriguez
authors: Huanliang
authors: H
authors: Liu
authors: Yu Dana
authors: YD
authors: Zhang
authors: John R
authors: JR
authors: Bethea
authors: Melvin C
authors: MC
authors: Gitlin
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use; D009392:Nephrectomy; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011184:Postoperative Period
chemical_list: D000701:Analgesics, Opioid; D053590:Interleukin 1 Receptor Antagonist Protein; D009020:Morphine