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beta1-Adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

Item Type:Article
Title:beta1-Adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?
Creators Name:Podlowski, S. and Wenzel, K. and Luther, H.P. and Mueller, J. and Bramlage, P. and Baumann, G. and Felix, S.B. and Speer, A. and Hetzer, R. and Koepke, K. and Hoehe, M.R. and Wallukat, G.
Abstract:A substantial body of evidence suggests involvement of the human {beta}1- adrenoceptor (β1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. {beta} 1-AR- mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402- Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different β1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.
Keywords:{Beta}1-Adrenoceptor, Dilated Cardiomyopathy, Single Nucleotide Polymorphisms
Source:Journal of Molecular Medicine
Page Range:87-93
Date:1 January 2000
Official Publication:https://doi.org/10.1007/s001090000080
PubMed:View item in PubMed

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