title: A polymorphism in the protein kinase C gene PRKCB is associated with α2-adrenoceptor-mediated vasoconstriction.
abstract: OBJECTIVE
  α2-Adrenoceptors (α2-AR) mediate both constriction and dilatation of blood vessels. There is considerable interindividual variability in dorsal hand vein (DHV) constriction responses to α2-AR agonist activation. Genetic factors appear to contribute significantly to this variation. The present study was designed to identify the genetic factors contributing toward the interindividual variability in α2-AR-mediated vascular constriction induced by the selective α2-AR agonist dexmedetomidine.
  
  
  METHODS
  DHV constriction responses to a local infusion of dexmedetomidine were assessed by measuring changes in vein diameter with a linear variable differential transformer. The outcome variable for constriction was log-transformed dexmedetomidine ED50. A genome-wide association study (GWAS) of 433 378 single-nucleotide polymorphisms (SNPs) was carried out for determining the sensitivity of DHV responses in 64 healthy Finnish individuals. Twenty SNPs were selected on the basis of the GWAS results and their associations with the ED50 of dexmedetomidine were tested in an independent North American study population of 68 healthy individuals.
  
  
  RESULTS
  In both study populations (GWAS and replication samples), the SNP rs9922316 in the gene for protein kinase C type β was consistently associated with dexmedetomidine ED50 for DHV constriction (unadjusted P=0.00016 for the combined population).
  
  
  CONCLUSIONS
  Genetic variation in protein kinase C type β may contribute toward the interindividual variation in DHV constriction responses to α2-AR activation by the agonist dexmedetomidine.
authors: Dept. of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.|Dept. of Surgery, Division of Neurosurgery, Turku University Hospital, Turku, Finland.|TYKSLAB, Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
authors: Jussi P
authors: JP
authors: Posti
authors: Finnish Institute for Molecular Medicine, Helsinki, Finland.
authors: Perttu
authors: P
authors: Salo
authors: Dept. of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.
authors: Saku
authors: S
authors: Ruohonen
authors: Dept. of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.
authors: Laura
authors: L
authors: Valve
authors: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors: Mordechai
authors: M
authors: Muszkat
authors: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors: Gbenga G
authors: GG
authors: Sofowora
authors: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors: Daniel
authors: D
authors: Kurnik
authors: Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors: C Michael
authors: CM
authors: Stein
authors: Finnish Institute for Molecular Medicine, Helsinki, Finland.
authors: Markus
authors: M
authors: Perola
authors: Dept. of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.|TYKSLAB, Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
authors: Mika
authors: M
authors: Scheinin
authors: Dept. of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.|Orion Corporation, Turku, Finland.
authors: Amir
authors: A
authors: Snapir
mesh_terms: D020927:Dexmedetomidine / Q000494:pharmacology; D005387:Finland; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011493:Protein Kinase C / Q000235:genetics*; D064546:Protein Kinase C beta; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012016:Reference Values; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D020927:Dexmedetomidine; D011493:Protein Kinase C; D064546:Protein Kinase C beta