title: Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in heart failure patients with a loss-of-function polymorphism of the presynaptic alpha2C-adrenergic receptor.
abstract: BACKGROUND
  Patients with a deletion of 4 consecutive amino acids in the gene encoding for the alpha(2C)-adrenergic receptor (alpha(2C)Del322-325) have an increased prevalence of clinical heart failure, worse clinical status, and a lower left ventricular ejection fraction compared with patients without this deletion. We postulated that patients with the alpha(2C)Del322-325 polymorphism would have a compensatory increase in norepinephrine uptake-1 transporter activity as measured by iodine 123 metaiodobenzylguanidine (MIBG).
  
  
  RESULTS
  Thirty-nine patients with heart failure related to idiopathic dilated cardiomyopathy were studied. Demographic characteristics, left ventricular ejection fraction, maximum oxygen consumption, exercise duration, and plasma norepinephrine levels did not differ between patients with the alpha(2C) receptor polymorphism (n = 9) and those without it (n = 30). Patients with the alpha(2C)Del322-325 polymorphism had significantly greater heart-to-mediastinum ratios of I-123 MIBG at 4 hours after tracer injection (1.60 +/- 0.19 vs 1.41 +/- 0.19, P =.0117) and greater background-corrected heart counts per pixel at 4 hours compared with patients without the polymorphism.
  
  
  CONCLUSIONS
  Patients with genetic impairment of the alpha(2C)-adrenergic receptor have augmented activity of the norepinephrine uptake-1 transporter as measured by I-123 MIBG. Further studies are needed to clarify the mechanism by which uptake-1 transporter activity is increased in this setting.
authors.affiliation: Division of Cardiology, University of Cincinnati, Ohio 45267-0542, USA. myron.gerson@uc.edu
authors.forename: Myron C
authors.initials: MC
authors.lastname: Gerson
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagoner
authors.forename: Nancy
authors.initials: N
authors.lastname: McGuire
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Liggett
mesh_terms: D019797:3-Iodobenzylguanidine; D002303:Cardiac Output, Low / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011110:Polymorphism, Genetic / Q000235:genetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2 / Q000172:deficiency / Q000235:genetics*; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000378:metabolism*
chemical_list: C547774:ADRA2C protein, human; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2; C493227:SLC6A2 protein, human; D027981:Symporters; D019797:3-Iodobenzylguanidine