title: The Gly16 Allele of the Gly16Arg Single-Nucleotide Polymorphism in the β₂-Adrenergic Receptor Gene Augments Perioperative Use of Vasopressors: A Retrospective Cohort Study.
abstract: BACKGROUND
  Arterial hypotension is frequent in patients undergoing anesthesia and may aggravate the outcome. Common genetic variations may influence the cardiovascular response to anesthesia. In this retrospective cohort study, we tested whether variation in the gene encoding the β2-adrenergic receptor (ADRB2) influences perioperative arterial blood pressure and consequently the use of vasopressors.
  
  
  METHODS
  Five hundred seventy-one Danish Caucasians undergoing neurosurgery were genotyped for 5 marker single-nucleotide polymorphisms (SNPs) within ADRB2 (Gly16Arg, Gln27Glu, Thr164Ile, Arg175Arg, and Gly351Gly). A pairwise tagging principle was used to identify ADRB2 haplotypes. Mean arterial blood pressure (MAP) was recorded in the supine awake state and, together with administration of vasopressors (ephedrine and/or phenylephrine), for 30 minutes after induction of general anesthesia (sevoflurane/remifentanil or propofol/remifentanil).
  
  
  RESULTS
  Four hundred thirteen (72%) patients received ephedrine and/or phenylephrine. Only baseline MAP (P < 0.001) and the Arg175Arg SNP (P = 0.01) were associated with nadir perioperative MAP. The Gly16Arg SNP but no other SNPs showed a trend toward an association with the amount of vasopressors used during anesthesia with Arg16 homozygotes receiving less ephedrine equivalents. The Arg16-Gln27-Thr164-Arg175-Gly351 haplotype was associated with approximately 13% lower vasopressor requirements than the most common Gly16-Glu27-Thr164-Arg175-Gly351 haplotype (P = 0.01).
  
  
  CONCLUSIONS
  Gly16 carriers received larger amounts of vasopressor compared with Arg16 homozygotes. This corresponds to previous studies demonstrating that the Gly16 allele in ADRB2 is associated with vasodilation and high cardiac output.
authors.affiliation: From the *Department of Neuroanesthesia, The Neuroscience Centre, †Department of Clinical Immunology, Centre of Clinical Investigation, and ‡Department of Anesthesia, The Abdominal Centre, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; and §Department of Neuroscience and Pharmacology, The Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.forename: Jonatan M
authors.initials: JM
authors.lastname: Staalsoe
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
authors.forename: Henning B
authors.initials: HB
authors.lastname: Nielsen
authors.forename: Niels V
authors.initials: NV
authors.lastname: Olsen
mesh_terms: D000328:Adult; D000368:Aged; D000768:Anesthesia, General / Q000009:adverse effects*; D062186:Arterial Pressure / Q000187:drug effects*; D004252:DNA Mutational Analysis; D003718:Denmark; D017558:Elective Surgical Procedures; D004809:Ephedrine / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007022:Hypotension / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D010597:Pharmacogenetics; D010641:Phenotype; D010656:Phenylephrine / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*; D044465:White People / Q000235:genetics
chemical_list: C553443:ADRB2 protein, human; D018343:Receptors, Adrenergic, beta-2; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D004809:Ephedrine