title: State of play of pharmacogenetics and personalized medicine in heart failure.
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.
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Parry
authors.forename: Alex S F
authors.initials: AS
authors.lastname: Doney
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Chim C
authors.initials: CC
authors.lastname: Lang
mesh_terms: D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009569:Nitric Oxide
keywords: Candidate genes; Genome-wide association study; Heart failure; Pharmacogenetics; Pharmacogenomics