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Previous Volume 347:1135-1142 October 10, 2002 Number 15 Next

Synergistic Polymorphisms of ß₁- and _2C-Adrenergic Receptors and the Risk of Congestive Heart Failure

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ABSTRACT

Background Sustained cardiac adrenergic stimulation has been implicated in the development and progression of heart failure. Release of norepinephrine is controlled by negative feedback from presynaptic ₂-adrenergic receptors, and the targets of the released norepinephrine on myocytes are ₁-adrenergic receptors. In transfected cells, a polymorphic _2C-adrenergic receptor (_2CDel322–325) has decreased function, and a variant of the ₁-adrenergic receptor (₁Arg389) has increased function. We hypothesized that this combination of receptor variants, which results in increased synaptic norepinephrine release and enhanced receptor function at the myocyte, would predispose persons to heart failure.

Methods Genotyping at these loci was performed in 159 patients with heart failure and 189 controls. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of heart failure.

Results Among black subjects, the adjusted odds ratio for heart failure among persons who were homozygous for _2CDel322–325 as compared with those with the other _2C-adrenergic receptor genotypes was 5.65 (95 percent confidence interval, 2.67 to 11.95; P<0.001). There was no increase in risk with ₁Arg389 alone. However, there was a marked increase in the risk of heart failure among persons who were homozygous for both variants (adjusted odds ratio, 10.11; 95 percent confidence interval, 2.11 to 48.53; P=0.004). The patients with heart failure did not differ from the controls in the frequencies of nine short tandem-repeat alleles. Among white subjects, there were too few who were homozygous for both polymorphisms to allow an adequate assessment of risk.

Conclusions The _2CDel322–325 and ₁Arg389 receptors act synergistically to increase the risk of heart failure in blacks. Genotyping at these two loci may be a useful approach for identification of persons at risk for heart failure or its progression, who may be candidates for early preventive measures.

Source Information

From the Divisions of Pulmonary Medicine (K.M.S., S.B.L.) and Cardiology (L.E.W.) and the Departments of Medicine and Molecular Genetics (S.B.L.), University of Cincinnati College of Medicine, Cincinnati; and the Department of Epidemiology, University of Michigan, Ann Arbor (A.M.L., S.L.R.K.).

Drs. Small and Wagoner contributed equally to the article.

Address reprint requests to Dr. Liggett at the University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0564, Cincinnati, OH 45267-0564, or at stephen.liggett{at}uc.edu.

Full Text of this Article

Related Letters:

Polymorphisms of Adrenergic Receptors and the Risk of Heart Failure
Meisel C., Köpke K., Roots I., Maitland M. L., Gomberg-Maitland M., Little J., Gwinn M., Khoury M., Kardia S. L.R., Levin A. M., Liggett S. B.
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N Engl J Med 2003; 348:468-470, Jan 30, 2003. Correspondence

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• Etzel, J. P., Rana, B. K., Wen, G., Parmer, R. J., Schork, N. J., O'Connor, D. T., Insel, P. A. (2005). Genetic Variation at the Human {alpha}2B-Adrenergic Receptor Locus: Role in Blood Pressure Variation and Yohimbine Response. Hypertension 45: 1207-1213 [Abstract] [Full Text]  
• Mann, D. L., Bristow, M. R. (2005). Mechanisms and Models in Heart Failure: The Biomechanical Model and Beyond. Circulation 111: 2837-2849 [Full Text]  
• Kaye, D., Esler, M. (2005). Sympathetic neuronal regulation of the heart in aging and heart failure. Cardiovasc Res 66: 256-264 [Abstract] [Full Text]  
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• Kaye, D. M., Smirk, B., Finch, S., Williams, C., Esler, M. D. (2004). Interaction between cardiac sympathetic drive and heart rate in heart failure: Modulation by adrenergic receptor genotype. J Am Coll Cardiol 44: 2008-2015 [Abstract] [Full Text]  
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• Pieske, B. (2004). Reverse remodeling in heart failure - fact or fiction?. Eur Heart J Suppl 6: D66-D78 [Abstract] [Full Text]  
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• Kansagra, S., List, J. (2004). The Clinical Relevance of Genomic Variation. JAMA 291: 1641-1641 [Full Text]  
• Kirstein, S. L., Insel, P. A. (2004). Autonomic Nervous System Pharmacogenomics: A Progress Report. Pharmacol. Rev. 56: 31-52 [Abstract] [Full Text]  
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• Keys, J.R., Koch, W.J. (2004). The Adrenergic Pathway and Heart Failure. Recent Prog Horm Res 59: 13-30 [Abstract] [Full Text]  
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• Feldman, A. M. (2003). The emerging role of pharmacogenomics in the treatment of patients with heart failure. Ann. Thorac. Surg. 76: S2246-2253 [Full Text]  
• Le Corvoisier, P., Park, H.-Y., Carlson, K. M., Marchuk, D. A., Rockman, H. A. (2003). Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy. Hum Mol Genet 12: 3097-3107 [Abstract] [Full Text]  
• Lohse, M. J., Engelhardt, S., Eschenhagen, T. (2003). What Is the Role of {beta}-Adrenergic Signaling in Heart Failure?. Circ. Res. 93: 896-906 [Abstract] [Full Text]  
• Chakir, K., Xiang, Y., Yang, D., Zhang, S.-J., Cheng, H., Kobilka, B. K., Xiao, R.-P. (2003). The Third Intracellular Loop and the Carboxyl Terminus of {beta}2-Adrenergic Receptor Confer Spontaneous Activity of the Receptor. Mol. Pharmacol. 64: 1048-1058 [Abstract] [Full Text]  
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• Anderson, J. L., Carlquist, J. F., Home, B. D., Muhlestein, J. B. (2003). Cardiovascular Pharmacogenomics: Current Status, Future Prospects. J CARDIOVASC PHARMACOL THER 8: 71-83 [Abstract]  
• Doevendans, P. A. (2003). Genetic Polymorphisms and Cardiac Failure. SEMIN CARDIOTHORAC VASC ANESTH 7: 23-29  
• Meisel, C., Kopke, K., Roots, I., Maitland, M. L., Gomberg-Maitland, M., Little, J., Gwinn, M., Khoury, M., Kardia, S. L.R., Levin, A. M., Liggett, S. B. (2003). Polymorphisms of Adrenergic Receptors and the Risk of Heart Failure. NEJM 348: 468-470 [Full Text]  
• (2002). Adrenergic-Receptor Polymorphisms May Predict CHF Risk. Journal Watch Cardiology 2002: 4-4 [Full Text]  
• Gottlieb, S. (2002). Genetic link explains greater prevalence of heart failure among black Americans. BMJ 325: 855-855 [Full Text]  
• Hajjar, R. J., MacRae, C. A. (2002). Adrenergic-Receptor Polymorphisms and Heart Failure. NEJM 347: 1196-1199 [Full Text]