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Erschienen in: Journal of Cardiovascular Translational Research 4/2019

12.02.2019 | Original Article

Association of Genetic Polymorphisms in the Beta-1 Adrenergic Receptor with Recovery of Left Ventricular Ejection Fraction in Patients with Heart Failure

verfasst von: Jasmine A. Luzum, Joseph D. English, Umair S. Ahmad, Jessie W. Sun, Benjamin D. Canan, Wolfgang Sadee, Joseph P. Kitzmiller, Philip F. Binkley

Erschienen in: Journal of Cardiovascular Translational Research | Ausgabe 4/2019

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Abstract

Two common genetic polymorphisms in the beta-1 adrenergic receptor (ADRB1 Ser49Gly [rs1801252] and Arg389Gly [rs1801253]) significantly affect receptor function in vitro. The objective of this study was to determine whether ADRB1 Ser49Gly and Arg389Gly are associated with recovery of left ventricular ejection fraction (LVEF) in patients with heart failure. Patients with heart failure and baseline LVEF ≤ 40% were genotyped (n = 98), and retrospective chart review assessed the primary outcome of LVEF recovery to ≥ 40%. Un/adjusted logistic regression models revealed that Ser49Gly, but not Arg389Gly, was significantly associated with LVEF recovery in a dominant genetic model. The adjusted odds ratio for Ser49 was 8.2 (95% CI = 2.1–32.9; p = 0.003), and it was the strongest predictor of LVEF recovery among multiple clinical variables. In conclusion, patients with heart failure and reduced ejection fraction that are homozygous for ADRB1 Ser49 were significantly more likely to experience LVEF recovery than Gly49 carriers.
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Literatur
3.
Zurück zum Zitat Teeter, W. A., Thibodeau, J. T., Rao, K., Brickner, M. E., Toto, K. H., Nelson, L. L., et al. (2012). The natural history of new-onset heart failure with a severely depressed left ventricular ejection fraction: Implications for timing of implantable cardioverter-defibrillator implantation. American Heart Journal, 164(3), 358–364. https://doi.org/10.1016/j.ahj.2012.06.009.CrossRefPubMed Teeter, W. A., Thibodeau, J. T., Rao, K., Brickner, M. E., Toto, K. H., Nelson, L. L., et al. (2012). The natural history of new-onset heart failure with a severely depressed left ventricular ejection fraction: Implications for timing of implantable cardioverter-defibrillator implantation. American Heart Journal, 164(3), 358–364. https://​doi.​org/​10.​1016/​j.​ahj.​2012.​06.​009.CrossRefPubMed
7.
9.
Zurück zum Zitat Rathz, D. A., Brown, K. M., Kramer, L. A., & Liggett, S. B. (2002). Amino acid 49 polymorphisms of the human [beta] 1-adrenergic receptor affect agonist-promoted trafficking. Journal of Cardiovascular Pharmacology, 39(2), 155–160.CrossRefPubMed Rathz, D. A., Brown, K. M., Kramer, L. A., & Liggett, S. B. (2002). Amino acid 49 polymorphisms of the human [beta] 1-adrenergic receptor affect agonist-promoted trafficking. Journal of Cardiovascular Pharmacology, 39(2), 155–160.CrossRefPubMed
10.
Zurück zum Zitat Liggett, S. B., Mialet-Perez, J., Thaneemit-Chen, S., Weber, S. A., Greene, S. M., Hodne, D., et al. (2006). A polymorphism within a conserved beta1-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proceedings of the National Academy of Sciences, 103(30), 11288–11293. https://doi.org/10.1073/pnas.0509937103.CrossRef Liggett, S. B., Mialet-Perez, J., Thaneemit-Chen, S., Weber, S. A., Greene, S. M., Hodne, D., et al. (2006). A polymorphism within a conserved beta1-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proceedings of the National Academy of Sciences, 103(30), 11288–11293. https://​doi.​org/​10.​1073/​pnas.​0509937103.CrossRef
11.
Zurück zum Zitat Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., et al. (2013). 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 62(16), e147–e239. https://doi.org/10.1016/j.jacc.2013.05.019.CrossRefPubMed Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., et al. (2013). 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 62(16), e147–e239. https://​doi.​org/​10.​1016/​j.​jacc.​2013.​05.​019.CrossRefPubMed
16.
Zurück zum Zitat Talameh, J., Garrand, A., Ghali, J., Oren, R. M., Dunlap, S., Bakel, A. V., et al. (2012). Beta-1 adrenergic receptor genotype Ser49Gly is associated with beta-blocker survival benefit in patients with heart failure. Journal of the American College of Cardiology, 59(13, Supplement), E861. https://doi.org/10.1016/S0735-1097(12)60862-6.CrossRef Talameh, J., Garrand, A., Ghali, J., Oren, R. M., Dunlap, S., Bakel, A. V., et al. (2012). Beta-1 adrenergic receptor genotype Ser49Gly is associated with beta-blocker survival benefit in patients with heart failure. Journal of the American College of Cardiology, 59(13, Supplement), E861. https://​doi.​org/​10.​1016/​S0735-1097(12)60862-6.CrossRef
17.
Zurück zum Zitat Levin, M. C., Marullo, S., Muntaner, O., Andersson, B., & Magnusson, Y. (2002). The myocardium-protective Gly-49 variant of the β1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. Journal of Biological Chemistry, 277(34), 30429–30435. https://doi.org/10.1074/jbc.M200681200.CrossRefPubMed Levin, M. C., Marullo, S., Muntaner, O., Andersson, B., & Magnusson, Y. (2002). The myocardium-protective Gly-49 variant of the β1-adrenergic receptor exhibits constitutive activity and increased desensitization and down-regulation. Journal of Biological Chemistry, 277(34), 30429–30435. https://​doi.​org/​10.​1074/​jbc.​M200681200.CrossRefPubMed
18.
Zurück zum Zitat Terra, S. G., Hamilton, K. K., Pauly, D. F., Lee, C. R., Patterson, J. H., Adams, K. F., et al. (2005). Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy. Pharmacogenetics and Genomics, 15(4), 227.CrossRefPubMed Terra, S. G., Hamilton, K. K., Pauly, D. F., Lee, C. R., Patterson, J. H., Adams, K. F., et al. (2005). Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy. Pharmacogenetics and Genomics, 15(4), 227.CrossRefPubMed
19.
Zurück zum Zitat de Groote, P., Helbecque, N., Lamblin, N., Hermant, X., Mc Fadden, E., Foucher-Hossein, C., et al. (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(3), 137–142. https://doi.org/10.1097/01213011-200503000-00001.CrossRefPubMed de Groote, P., Helbecque, N., Lamblin, N., Hermant, X., Mc Fadden, E., Foucher-Hossein, C., et al. (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(3), 137–142. https://​doi.​org/​10.​1097/​01213011-200503000-00001.CrossRefPubMed
20.
Zurück zum Zitat Nonen, S., Okamoto, H., Fujio, Y., Takemoto, Y., Yoshiyama, M., Hamaguchi, T., et al. (2008). Polymorphisms of norepinephrine transporter and adrenergic receptor α1D are associated with the response to β-blockers in dilated cardiomyopathy. The Pharmacogenomics Journal, 8(1), 78–84. https://doi.org/10.1038/sj.tpj.6500450.CrossRefPubMed Nonen, S., Okamoto, H., Fujio, Y., Takemoto, Y., Yoshiyama, M., Hamaguchi, T., et al. (2008). Polymorphisms of norepinephrine transporter and adrenergic receptor α1D are associated with the response to β-blockers in dilated cardiomyopathy. The Pharmacogenomics Journal, 8(1), 78–84. https://​doi.​org/​10.​1038/​sj.​tpj.​6500450.CrossRefPubMed
21.
Zurück zum Zitat Chen, L., Meyers, D., Javorsky, G., Burstow, D., Lolekha, P., Lucas, M., et al. (2007). Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol. Pharmacogenetics and Genomics, 17(11), 941. https://doi.org/10.1097/FPC.0b013e3282ef7354.CrossRefPubMed Chen, L., Meyers, D., Javorsky, G., Burstow, D., Lolekha, P., Lucas, M., et al. (2007). Arg389Gly-beta1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol. Pharmacogenetics and Genomics, 17(11), 941. https://​doi.​org/​10.​1097/​FPC.​0b013e3282ef7354​.CrossRefPubMed
22.
Zurück zum Zitat Perez, J. M., Rathz, D. A., Petrashevskaya, N. N., Hahn, H. S., Wagoner, L. E., Schwartz, A., et al. (2003). [Beta]1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nature Medicine, 9(10), 1300. https://doi.org/10.1038/nm930.CrossRef Perez, J. M., Rathz, D. A., Petrashevskaya, N. N., Hahn, H. S., Wagoner, L. E., Schwartz, A., et al. (2003). [Beta]1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Nature Medicine, 9(10), 1300. https://​doi.​org/​10.​1038/​nm930.CrossRef
23.
Zurück zum Zitat Luo, M., Bi, Y., & Xu, Y. X. (2007). Effects of metoprolol on beta1 adrenergic receptor polymorphism and receptor density in urban Chinese patients with heart failure. Chinese Medical Journal, 120(19), 1720–1723.CrossRefPubMed Luo, M., Bi, Y., & Xu, Y. X. (2007). Effects of metoprolol on beta1 adrenergic receptor polymorphism and receptor density in urban Chinese patients with heart failure. Chinese Medical Journal, 120(19), 1720–1723.CrossRefPubMed
25.
Zurück zum Zitat Metra, M., Covolo, L., Pezzali, N., Zacà, V., Bugatti, S., Carlo, L., et al. (2010). Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovascular Drugs and Therapy, 24(1), 49–60. https://doi.org/10.1007/s10557-010-6220-5.CrossRefPubMed Metra, M., Covolo, L., Pezzali, N., Zacà, V., Bugatti, S., Carlo, L., et al. (2010). Role of beta-adrenergic receptor gene polymorphisms in the long-term effects of beta-blockade with carvedilol in patients with chronic heart failure. Cardiovascular Drugs and Therapy, 24(1), 49–60. https://​doi.​org/​10.​1007/​s10557-010-6220-5.CrossRefPubMed
29.
Metadaten
Titel
Association of Genetic Polymorphisms in the Beta-1 Adrenergic Receptor with Recovery of Left Ventricular Ejection Fraction in Patients with Heart Failure
verfasst von
Jasmine A. Luzum
Joseph D. English
Umair S. Ahmad
Jessie W. Sun
Benjamin D. Canan
Wolfgang Sadee
Joseph P. Kitzmiller
Philip F. Binkley
Publikationsdatum
12.02.2019
Verlag
Springer US
Erschienen in
Journal of Cardiovascular Translational Research / Ausgabe 4/2019
Print ISSN: 1937-5387
Elektronische ISSN: 1937-5395
DOI
https://doi.org/10.1007/s12265-019-09866-5

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