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β-Adrenoceptor polymorphisms

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Abstract

There can be no doubt that β1-, β2- and β3-adrenoceptor genes have genetic polymorphisms. Two single nucleotide polymorphisms have been described for the β1- (Ser49Gly; Gly389Arg), three for the β2- (Arg16Gly; Gln27Glu; Thr164Ile) and one for the β3-adrenoceptor subtype (Trp64Arg) that might be of functional importance. The possibility that changes in expression or properties of the β-adrenoceptors due to single nucleotide polymorphisms might have phenotypic consequences influencing their cardiovascular or metabolic function or may contribute to the pathophysiology of several disorders like hypertension, congestive heart failure, asthma or obesity is an idea that has attracted much interest during the last 10 years. At present, it appears that these β-adrenoceptor polymorphisms are very likely not disease-causing genes, but might be risk factors, might modify disease and/or might influence progression of disease. The aim of this review is to provide an overview of the functional consequences of such β-adrenoceptor polymorphisms in vitro, ex vivo and in vivo.

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Authors and Affiliations

  1. Depts. of Pathophysiology and Nephrology, University of Essen School of Medicine, IG I., 9.OG, Hufelandstrasse 55, 45147, Essen, Germany

    K. Leineweber, H. Bruck & O.-E. Brodde

  2. Department of Pediatric Nephrology, University of Essen School of Medicine, 45147, Essen, Germany

    R. Büscher

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  1. K. Leineweber
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Appendix

Appendix

Tables 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10.

Table 1 Single nucleotide polymorphisms in the three β-adrenoceptor (AR) subtypes. (SNP single nucleotide polymorphism, AA amino acid, UTR untranslated region, BUP beta-upstream peptide)
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Table 2 In vitro β1-AR phenotypes (ISO isoprenaline, AC adenylyl cyclase, G s stimulatory G protein)
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Table 3 Ex vivo β1-AR phenotypes. (NA noradrenaline, cAMP cyclic AMP)
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Table 4 In vivo β1-AR phenotypes
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Table 5 In vitro β2-AR phenotypes
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Table 6 Ex vivo β2-AR phenotypes (HASM human airway smooth muscle TER terbutaline, SALB salbutamol, HLM human lung mast cells)
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Table 7 In vivo β2-AR phenotype. (CHF chronic heart failure, V̇O2 maximum pulmonary O2 uptake rate)
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Table 8 In vitro β3-AR phenotype. (A adrenaline)
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Table 9 Ex vivo β3-AR phenotype
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Table 10 In vivo β3-AR phenotype
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Leineweber, K., Büscher, R., Bruck, H. et al. β-Adrenoceptor polymorphisms. Naunyn-Schmiedeberg's Arch Pharmacol 369, 1–22 (2004). https://doi.org/10.1007/s00210-003-0824-2

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