Affordable Access

deepdyve-link
Publisher Website

State of play of pharmacogenetics and personalized medicine in heart failure.

Authors
  • Parry, Helen M
  • Doney, Alex S F
  • Palmer, Colin N A
  • Lang, Chim C
Type
Published Article
Journal
Cardiovascular therapeutics
Publication Date
Dec 01, 2013
Volume
31
Issue
6
Pages
315–322
Identifiers
DOI: 10.1111/1755-5922.12030
PMID: 23480579
Source
Medline
Keywords
License
Unknown

Abstract

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.

Report this publication

Statistics

Seen <100 times