Universität zu Köln

Leineweber, Kirsten, Frey, Ulrich H., Tenderich, Gero, Toliat, Mohammad Reza, Zittermann, Armin, Nuernberg, Peter, Koerfer, Reiner, Siffert, Winfried and Heusch, Gerd (2010). The Arg16Gly-beta(2)-adrenoceptor single nucleotide polymorphism: exercise capacity and survival in patients with end-stage heart failure. Naunyn-Schmiedebergs Arch. Pharmacol., 382 (4). S. 357 - 366. NEW YORK: SPRINGER. ISSN 1432-1912

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Abstract

Heart failure (HF) is characterized by impaired myocardial beta-adrenergic signal transduction. Single nucleotide polymorphisms (SNPs) within the beta(1)- (Ser49Gly, Arg389Gly) and beta(2)-adrenoceptor (Arg16Gly, Gln27Glu, Thr164Ile) have been associated with alterations in adrenoceptor (AR) function sensitivity in vitro and in vivo and possibly contribute to HF progression. The present study evaluated the relation of those SNPs to morbidity and mortality in patients with end-stage HF. A total of 226 patients with end-stage HF (ejection fraction a parts per thousand currency sign35%) were genotyped for the two beta(1)AR SNPs and the three beta(2)AR SNPs. Outcome (death, heart transplantation (HTX)) was determined from May 2003 to June 2004. Heart rate, systolic and diastolic blood pressure, and peak oxygen uptake were measured during graded treadmill exercise. Left ventricular end-diastolic and end-systolic diameters, ejection fraction, and fractional shortening at rest were measured using two-dimensional echocardiography. Minor allele frequencies were 0.12 for Gly49 and 0.27 for Gly389 (beta(1)AR) and 0.37 for Arg16, 0.43 for Glu27 and 0.01 for Ile164 (beta(2)AR). During follow-up, 45 patients died (20%), and 27 patients underwent HTX (12%). No significant differences in the incidence or in the time-to-endpoint of death and HTX between genotypes of the different SNPs within the beta(1)- and beta(2)AR were detected. However, patients carrying the Arg16-beta(2)AR tended to have lower exercise capacity and a higher probability for death/HTX within 45 months (survival proportion 46%) than patients carrying the Gly16Gly-beta(2)AR (survival proportion 64%). In conclusion, the Arg16Gly-beta(2)AR might impact on exercise capacity and outcome in end-stage heart failure.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Leineweber, Kirsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Frey, Ulrich H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tenderich, Gero UNSPECIFIED UNSPECIFIED UNSPECIFIED Toliat, Mohammad Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Zittermann, Armin UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Koerfer, Reiner UNSPECIFIED UNSPECIFIED UNSPECIFIED Siffert, Winfried UNSPECIFIED UNSPECIFIED UNSPECIFIED Heusch, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-496051
DOI:	10.1007/s00210-010-0548-z
Journal or Publication Title:	Naunyn-Schmiedebergs Arch. Pharmacol.
Volume:	382
Number:	4
Page Range:	S. 357 - 366
Date:	2010
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1912
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ADRENERGIC-RECEPTOR POLYMORPHISMS; HUMAN BETA(2)-ADRENERGIC RECEPTOR; HUMAN BETA(1)-ADRENERGIC RECEPTOR; IN-VIVO; CARDIOVASCULAR-DISEASES; DILATED CARDIOMYOPATHY; BLOOD-PRESSURE; G-PROTEIN; DESENSITIZATION; GENE Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49605