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

  • Jasmine A. LuzumEmail author
  • Joseph D. English
  • Umair S. Ahmad
  • Jessie W. Sun
  • Benjamin D. Canan
  • Wolfgang Sadee
  • Joseph P. Kitzmiller
  • Philip F. Binkley
Original Article


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.


Beta-1 adrenergic receptor Genetics Polymorphism Beta-blocker Heart failure Left ventricular ejection fraction 



Gene for the beta-1 adrenergic receptor


American Heart Association


American College of Cardiology




Body mass index


Centre d’Etude du Polymorphism Humain lymphoblastoid cell lines


Confidence interval


United States Food and Drug Administration




Heart failure


Heart failure with preserved ejection fraction


Heart failure with reduced ejection fraction


Left ventricular ejection fraction


New York Heart Association


Odds ratio


Systolic blood pressure




Compliance with Ethical Standards



Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Studies

No animal studies were carried out by the authors for this article.

Clinical Relevance

These findings from a small study at a single site need to be replicated in a larger study of multiple sites to be clinically relevant. The potential clinical relevance is that a patient’s ADRB1 Ser49Gly (rs1801252) genotype may be a predictor of whether or not the patient with HFrEF will have recovery of their LVEF to ≥ 40%. This genotype was the strongest predictor of LVEF recovery, even compared to multiple clinical variables. Thus, if validated, HFrEF patients that are ADRB1 Gly49 carriers may need additional monitoring or therapies compared to Ser49 homozygotes.

Supplementary material

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12265_2019_9866_MOESM3_ESM.docx (15 kb)
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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical PharmacyUniversity of Michigan College of PharmacyAnn ArborUSA
  2. 2.Department of Biological Chemistry and PharmacologyOhio State University College of MedicineColumbusUSA
  3. 3.Heart and Vascular InstituteSumma Health SystemAkronUSA
  4. 4.Division of Cardiovascular Medicine, Department of Internal MedicineOhio State University College of MedicineColumbusUSA
  5. 5.Center for PharmacogenomicsOhio State University College of MedicineColumbusUSA
  6. 6.Department of Physiology and Cell BiologyOhio State University College of MedicineColumbusUSA

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