Chronic heart failure: beta-blockers and pharmacogenetics.
OBJECTIVE
The European Society of Cardiology recommends that beta-blockers should be considered for treating all patients with stable, mild, moderate, or severe heart failure (HF) who are receiving standard treatment, unless there is a contraindication. Despite the significant benefit of the drug, there is widespread recognition of patient-to-patient variability in drug response. The genetic determinants of responses to drugs have important implications for the clinical course and management of HF. Pharmacogenetics (PGt) has drawn great attention for its potential to redirect personal care and public health paradigms. The aim of this review was to gather information on PGt of beta-blockers in HF treatment.


METHODS
We searched for articles related to PGt of beta-blockers in the PubMed database and attempted to cover all related articles.


RESULTS
Several genetic polymorphisms affecting proteins in the beta-adrenergic receptor signaling pathway have been proposed as modifiers of HF risk. The most relevant of these to this review is the pharmacogenetic interactions between the genetic variants of catecholamine receptors or their effectors and beta-blockade for the treatment of HF.


CONCLUSIONS
Interindividual variability of responsiveness to beta-blockers can be explained by PGt data of adrenaline-related genes. To demonstrate that pharmacogenetic intervention produces successful individualized beta-blocker treatment for HF patients, prospective, randomized, and pharmacogenomics (PGx)-based clinical trials are required. Our assessment is that we are already at a turning point in the history of clinical pharmacology.
Department of Clinical Pharmacology & Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. azuma@phs.osaka-u.ac.jp
Junichi
J
Azuma
Shinpei
S
Nonen
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D002908:Chronic Disease; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D054768:G-Protein-Coupled Receptor Kinases / Q000235:genetics; D006333:Heart Failure / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics; D018579:Patient Selection; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D017410:Practice Guidelines as Topic; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011943:Receptors, Adrenergic, beta; C493227:SLC6A2 protein, human; D003577:Cytochrome P-450 Enzyme System; D054768:G-Protein-Coupled Receptor Kinases; D007703:Peptidyl-Dipeptidase A