Skip to main content
Log in

Is there a role of the Thr164Ile-β2-adrenoceptor polymorphism for the outcome of chronic heart failure?

  • ORIGINAL CONTRIBUTION
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Objective

The Thr164Ile-β2-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-β2AR polymorphism exhibit much more rapid progression to death or heart transplantation (HTX) than CHF-patients carrying the homozygous Thr164-β2AR. This study aimed to further evaluate the role of the Thr164Ile-β2AR in CHF. For this we hypothesized that the Thr164Ile-β2AR variant should be more abundant in HTX-patients than in patients with stable CHF or healthy controls.

Methods and Results

We genotyped 309 HTX-patients, 520 stable CHF-patients and 328 healthy controls for the three β2AR variants Arg16Gly, Gln27Glu and Thr164Ile. The prevalence of the Thr164Ile-β2AR 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-β2AR 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-β2AR in CHF remains questionable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brodde O-E, Bruck H, Leineweber K (2006) Cardiac adrenoceptors: physiological and pathophysiological relevance. J Pharmacol Sci 100: (in press)

  2. Brodde O-E, Büscher R, Tellkamp R, Radke J, Dhein S, Insel PA (2001) Blunted cardiac responses to receptor activation in subjects with Thr164Ile β2-adrenoceptors. Circulation 103:1048–1050

    PubMed  CAS  Google Scholar 

  3. Brodde O-E, Leineweber K (2005) β2-Adrenoceptor gene polymorphisms. harmacogenetics and Genomics 15:267–275

    CAS  Google Scholar 

  4. Brodde O-E, Michel MC (1999) Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev 51:651–689

    PubMed  CAS  Google Scholar 

  5. Bruck H, Leineweber K, Büscher R, Ulrich A, Radke J, Insel PA, Brodde O-E (2003) The Gln27Glu β2-adrenoceptor polymorphism slows the onset of desensitization of cardiac functional responses in vivo. Pharmacogenetics 13:59–66

    Article  PubMed  CAS  Google Scholar 

  6. Bruck H, Leineweber K, Park J, Weber M, Heusch G, Philipp T, Brodde O-E (2005) Human β2-adrenoceptor gene haplotypes and venodilation in vivo. Clin Pharmacol Ther 78:232–238

    Article  PubMed  CAS  Google Scholar 

  7. Bruck H, Leineweber K, Ulrich A, Radke J, Heusch G, Philipp T, Brodde O-E (2003) Thr164Ile polymorphism of the human β2-adrenoceptor exhibits blunted desensitization of cardiac functional responses in vivo. Am J Physiol Heart Circ Physiol 285:H2034–H2038

    PubMed  CAS  Google Scholar 

  8. De Groote P, Helbecque N, Lamblin N, Hermant X, McFadden E, Foucher-Hossein C, Amouyel P, Dallongeville J, Bauters C (2005) Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure. Pharmacogenetics and Genomics 15:137–142

    Article  PubMed  CAS  Google Scholar 

  9. Dewar JC, Wheatley AP, Venn A, Morrison JF, Britton J, Hall IP (1998) β2-Adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population. Clin Exp Allergy 28:442–448

    Article  PubMed  CAS  Google Scholar 

  10. Dishy V, Landau R, Sofowora G, Xie HG, Smiley RM, Kim RB, Byrne DW, Wood AJ, Stein CM (2004) β2-Adrenoceptor polymorphism is associated with markedly decreased vasodilator and increased vasoconstrictor sensitivity in vivo. Pharmacogenetics 14:517–522

    Article  PubMed  CAS  Google Scholar 

  11. Forleo C, Resta N, Sorrentino S, Guida P, Manghisi A, De Luca V, Romito T, Iacoviello M, De Tommasi E, Troisi F, Rizzon B, Guanti G, Rizzon P, Pitzalies MV (2004) Association of β-adrenergic receptor polymorphisms and progression of heart failure in patients with idiopathic dilated cardiomyopathy. Am J Med 117:451–458

    Article  PubMed  CAS  Google Scholar 

  12. Green SA, Cole G, Jacinto M, Innes M, Liggett SB (1993) A polymorphism of the human β2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 268:23116–23121

    PubMed  CAS  Google Scholar 

  13. Green SA, Turki J, Innes M, Liggett SB (1994) Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33:9414–9419

    Article  PubMed  CAS  Google Scholar 

  14. Guimaraes S, Moura D (2001) Vascular adrenoceptors: an update. Pharmacol Rev 53:319–356

    PubMed  CAS  Google Scholar 

  15. Heckbert SR, Hindorff LA, Edwards KL, Psaty BM, Lumley T, Siscovick DS, Tang Z, Durda JP, Kronmal RA, Tracy RP (2003) β-Adrenergic polymophisms and risk of incident cardiovascular events in the elderly. Circulation 107:2021–2024

    Article  PubMed  CAS  Google Scholar 

  16. Liggett SB, Wagoner LE, Craft LL, Hornung RW, Hoit BD, McIntosh TC, Walsh RA (1998) The Ile164 β2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 102:1534–1539

    Article  PubMed  CAS  Google Scholar 

  17. Turki J, Lorenz JN, Green SA, Donnelly ET, Jacinto M, Liggett SB (1996) Myocardial signaling defects and impaired cardiac function of a human β2-adrenergic receptor polymorphism expressed in transgenic mice. Proc Natl Acad Sci USA 93:10483–10488

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Otto-Erich Brodde PhD.

Additional information

Prof. Dr. T. Eschenhagen, Hamburg, Germany, served as guest editor for the manuscript and was responsible for all editorial decisions, including the selection of reviewers. This policy applies to all manuscripts with authors from the editor’s institution.

Kirsten Leineweber and Gero Tenderich contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leineweber, K., Tenderich, G., Wolf, C. et al. Is there a role of the Thr164Ile-β2-adrenoceptor polymorphism for the outcome of chronic heart failure?. Basic Res Cardiol 101, 479–484 (2006). https://doi.org/10.1007/s00395-006-0601-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-006-0601-8

Key words

Navigation