title: Is there a role of the Thr164Ile-beta(2)-adrenoceptor polymorphism for the outcome of chronic heart failure?
abstract: OBJECTIVE
  The Thr164Ile-beta(2)-adrenoceptor (AR) polymorphism exhibits lower affinities for catecholamines and reduced basal and agonist-stimulated adenylyl cyclase activity in vitro. It has been suggested that patients with chronic heart failure (CHF) due to ischemic or dilated cardiomyopathy carrying the Thr164Ile-beta(2)AR polymorphism exhibit much more rapid progression to death or heart transplantation (HTX) than CHF-patients carrying the homozygous Thr164-beta(2)AR. This study aimed to further evaluate the role of the Thr164Ile-beta(2)AR in CHF. For this we hypothesized that the Thr164Ile-beta(2)AR variant should be more abundant in HTX-patients than in patients with stable CHF or healthy controls.
  
  
  RESULTS
  We genotyped 309 HTX-patients, 520 stable CHF-patients and 328 healthy controls for the three beta(2)AR variants Arg16Gly, Gln27Glu and Thr164Ile. The prevalence of the Thr164Ile-beta(2)AR variant was not considerably different in HTX-patients (2.3%) from that in CHF-patients (1.9%) or healthy controls (2.1%). Similarly, the frequency of the minor Ile164-allele was f(-)=0.0106 in HTX-patients, f(-)=0.0096 in CHF-patients and f(-)=0.0113 in healthy controls.
  
  
  CONCLUSIONS
  The prevalence of the hypofunctional Thr164Ile-beta(2)AR variant and the frequency of the Ile164-allele were almost identical in CHF-patients, who had undergone HTX, with those in patients with stable CHF or in healthy controls. Thus, the role of the Thr164Ile-beta(2)AR in CHF remains questionable.
authors.affiliation: Department of Pathophysiology, University of Essen School of Medicine, Hufelandstr. 55, 45147 Essen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Leineweber
authors.forename: Gero
authors.initials: G
authors.lastname: Tenderich
authors.forename: Christina
authors.initials: C
authors.lastname: Wolf
authors.forename: Sören
authors.initials: S
authors.lastname: Wagner
authors.forename: Armin
authors.initials: A
authors.lastname: Zittermann
authors.forename: Miriam
authors.initials: M
authors.lastname: Elter-Schulz
authors.forename: Reiner
authors.initials: R
authors.lastname: Moog
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
authors.forename: Heinz-Günther
authors.initials: HG
authors.lastname: Jakob
authors.forename: Reiner
authors.initials: R
authors.lastname: Körfer
authors.forename: Thomas
authors.initials: T
authors.lastname: Philipp
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
authors.forename: Otto-Erich
authors.initials: OE
authors.lastname: Brodde
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002303:Cardiac Output, Low / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D016027:Heart Transplantation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000502:physiology
chemical_list: D018343:Receptors, Adrenergic, beta-2