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Pharmacogenomics of Heart Failure

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Pharmacogenomics in Drug Discovery and Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1175))

Abstract

The combination of angiotensin-converting enzyme (ACE) inhibitors and β-adrenergic receptor (βAR) blockers remains the essential component of heart failure (HF) pharmacotherapy. However, individual patient responses to these pharmacotherapies vary widely. The variability in response cannot be explained entirely by clinical characteristics, and genetic variation may play a role. The purpose of this chapter is to examine the current knowledge in the field of beta-blocker and ACE inhibitor pharmacogenetics in HF. β-blocker and ACE inhibitor pharmacogenetic studies performed in patients with HF were identified from the PubMed database from 1966 to July 2011. Thirty beta-blocker and 10 ACE inhibitor pharmacogenetic studies in patients with HF were identified.

The ACE deletion variant was associated with greater survival benefit from ACE inhibitors and beta-blockers compared with the ACE insertion. Ser49 in the β1AR, the insertion in the α2CAR, and Gln41 in G protein-coupled receptor (GPCR) kinase (GRK)-5 are associated with greater survival benefit from β-blockers, compared with Gly49, the deletion, and Leu41, respectively. However, many of these associations have not been validated. The HF pharmacogenetic literature is still in its very early stages, but there are promising candidate genetic variants that may identify which HF patients are most likely to benefit from beta-blockers and ACE inhibitors and patients that may require additional therapies.

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Acknowledgements

Dr. Lymperopoulos is supported by a Scientist Development Grant (SDG) award from the American Heart Association (09SDG2010138, National Center). No other disclosure to report.

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  1. Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 S. University Dr., HPD (Terry) Bldg/Room 1338, 33328-2018, Ft. Lauderdale, FL, USA

    Anastasios Lymperopoulos & Faren French

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  1. Anastasios Lymperopoulos
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  2. Faren French
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Correspondence to Anastasios Lymperopoulos .

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  1. PharmTao, Santa Clara, California, USA

    Qing Yan

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Lymperopoulos, A., French, F. (2014). Pharmacogenomics of Heart Failure. In: Yan, Q. (eds) Pharmacogenomics in Drug Discovery and Development. Methods in Molecular Biology, vol 1175. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0956-8_10

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  • DOI: https://doi.org/10.1007/978-1-4939-0956-8_10

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0955-1

  • Online ISBN: 978-1-4939-0956-8

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