title: Genetic tailoring of pharmacotherapy in heart failure: optimize the old, while we wait for something new.
abstract: BACKGROUND
  The combination of angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic receptor 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 review is to examine our current state of understanding of beta-blocker and ACE inhibitor pharmacogenetics in HF.
  
  
  RESULTS
  Beta-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 beta-1 adrenergic receptor, the insertion in the alpha-2C adrenergic receptor, and Gln41 in G-protein-coupled receptor kinase 5 are associated with greater survival benefit from beta-blockers, compared with Gly49, the deletion, and Leu41, respectively. However, many of these associations have not been validated.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, USA.
authors.forename: Jasmine A
authors.initials: JA
authors.lastname: Talameh
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.forename: J Herbert
authors.initials: JH
authors.lastname: Patterson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D017353:Gene Deletion; D014644:Genetic Variation; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008790:Metoprolol / Q000627:therapeutic use; D016254:Mutagenesis, Insertional; D057285:Precision Medicine; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol