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Genetic polymorphisms in ADRB2 and ADRB1 are associated with differential survival in heart failure patients taking β-blockers

The Pharmacogenomics Journal volume 22, pages 62–68 (2022)Cite this article

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Abstract

Single nucleotide polymorphisms (SNPs) have been associated with differential beta-blocker (BB) effects on heart rate, blood pressure, and left ventricular ejection fraction in various patient populations. This study aimed to determine if SNPs previously associated with BB response are also associated with differential survival in heart failure (HF) patients receiving BBs. HF patient data were derived from electronic health records and the Social Security Death Index. Associations and interactions between BB dose, SNP genotype, and the outcome of death were assessed using a Cox proportional-hazard model adjusting for covariates known to be associated with differential survival in HF patients. Two SNPs, ADRB1 Arg389Gly and ADRB2 Glu27Gln, displayed significant interactions (Pint = 0.043 and Pint = 0.017, respectively) with BB dose and their association with mortality. Our study suggests that ADRB2 27Glu and ADRB1 389Arg may confer a larger survival benefit with higher BB doses in patients with HF.

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Fig. 1: Adjusted Kaplan–Meier curves for Gln27Glu (in ADRB2) genotype associations with all-cause mortality in the PGx comprehensive model by BB dose levels.
Fig. 2: Adjusted Kaplan–Meier curves for Arg389Gly (in ADRB1) genotype associations with all-cause mortality in the PGx comprehensive model, by BB dose levels.
Fig. 3: Adjusted Kaplan–Meier curves for polygenic response allele associations with all-cause mortality in the PGx comprehensive model, by BB dose levels.

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Acknowledgements

This project was funded in part by the University of Illinois at Chicago Office of the Vice Chancellor for Research as well as American Heart Association Midwest Affiliate Scientist Development Grant 0335361Z (LHC), NIH/NIA R03 AG033381 (LHC), NIH/NHLBI R01 HL141281 (AAD), and NIH/NIGMS K23 GM112014 (JDD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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  1. These authors contributed equally: Leonardo A. Guerra, Christelle Lteif.

Authors and Affiliations

  1. Center for Pharmacogenomics and Precision Medicine, Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA

    Leonardo A. Guerra, Christelle Lteif, Caitrin W. McDonough, Leanne Dumeny, Larisa H. Cavallari & Julio D. Duarte

  2. Tabula Rasa HealthCare Precision Pharmacotherapy R&D Institute, Orlando, FL, USA

    Meghan J. Arwood

  3. Genetics and Genomics, Genetics Institute, University of Florida, Gainesville, FL, USA

    Leanne Dumeny

  4. Krannert Institute of Cardiology, Department of Medicine, Indiana University, Indianapolis, IN, USA

    Ankit A. Desai

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Contributions

JDD conceived the work; JDD and CL designed the project; MJA, AAD, LHC, and JDD collected the data; LAG, LD, CM, and CL completed the analysis; LAG and CL wrote the manuscript; MJA, AAD, LHC, CM, LD, and JDD edited the manuscript.

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Correspondence to Julio D. Duarte.

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Guerra, L.A., Lteif, C., Arwood, M.J. et al. Genetic polymorphisms in ADRB2 and ADRB1 are associated with differential survival in heart failure patients taking β-blockers. Pharmacogenomics J 22, 62–68 (2022). https://doi.org/10.1038/s41397-021-00257-1

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