State of Play of Pharmacogenetics and Personalized Medicine in Heart Failure

Summary Heart failure is a common disease with high levels of morbidity and mortality. A large body of evidence guiding treatment shows prognostic benefit with beta‐blockers and angiotensin‐converting enzyme inhibitors, while diuretics are commonly prescribed for symptomatic benefit. Wide variation...

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Bibliographic Details
Published in:Cardiovascular therapeutics 2013-12, Vol.31 (6), p.315-322
Main Authors: Parry, Helen M., Doney, Alex S.F., Palmer, Colin N.A., Lang, Chim C.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Candidate genes
Cardiology. Vascular system
Cardiovascular system
Enzymes
Genetic Variation
Genome-Wide Association Study
Heart
Heart failure
Heart Failure - drug therapy
Heart Failure - genetics
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Humans
Medical sciences
Mortality
Nitric Oxide - physiology
Pharmacogenetics
Pharmacogenomics
Pharmacology. Drug treatments
Polymorphism, Single Nucleotide
Precision Medicine
Receptors, Adrenergic, beta-1 - genetics
Receptors, Adrenergic, beta-2 - genetics
Renin-Angiotensin System - physiology
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Summary:Summary Heart failure is a common disease with high levels of morbidity and mortality. A large body of evidence guiding treatment shows prognostic benefit with beta‐blockers and angiotensin‐converting enzyme inhibitors, while diuretics are commonly prescribed for symptomatic benefit. Wide variation in drug response between clinically similar patients is a significant problem. Evidence suggests this may have a genetic component. Variation in candidate genes including the beta‐1, beta‐2, and alpha‐2 adrenergic receptors, the renin–angiotensin–aldosterone pathway and genes involved in renal electrolyte handling with diuretics may be important. Single‐nucleotide polymorphisms (SNPs) potentially influencing drug response include the Arg 389 Gly variant and the Ser 49 Gly variant in the beta‐1 adrenergic receptor, the Arg 16 Gly, Gln 27 Glu, and Thr 164 Ile polymorphisms within the beta‐2 adrenergic receptor, an insertion at the 287th base pair in the angiotensin‐converting enzyme and the Gly 264 Ala mutation in the sodium chloride co‐transporter. However, research addressing the clinical significance of these polymorphisms has yielded conflicting results that have had no influence on clinical practice. Genome‐wide association studies may provide an alternative approach to discovering genetic variations influencing drug response, a relatively unchartered area in heart failure management. If future work in this area produces a strong case that variation in drug response has a specific and clinically meaningful genetic component, this could be used to guide drug dosing based on genotype; a step forward in the journey toward personally tailored medicine.
ISSN:1755-5914
1755-5922
DOI:10.1111/1755-5922.12030