title: Cardiovascular pharmacogenomics: expectations and practical benefits.
abstract: Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Pharmacogenomics is the study of genetic determinants of interindividual variation in drug response and aims to facilitate personalized medicine, through genotype-informed drug and dose selection, to maximize drug efficacy and/or minimize adverse drug reactions. Despite high expectations, no cardiovascular pharmacogenomic association is currently in widespread clinical practice; evidential, logistical, financial, and knowledge implementation barriers exist. Nevertheless, VKORC1, CYP2C9, and CYP4F2 variants have been associated with warfarin dose requirements, and CYP2C19 variants have been associated with perturbed antiplatelet response to clopidogrel. However, at present, controversy exists over the clinical utility of these genetic associations. There is an increased risk of simvastatin-induced muscle toxicity in SLCO1B1*5 carriers, ADRB1 and ADRA2C polymorphisms are associated with differential response to bucindolol, and rare congenital arrhythmia gene variants have been identified in drug-induced torsade de pointes. Practical benefits are still anticipated, but much work remains.
authors: 1] The Wolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK [2] Clinical Pharmacology, The Royal Liverpool University Hospital, Liverpool, UK.
authors: R M
authors: RM
authors: Turner
authors: 1] The Wolfson Centre for Personalised Medicine, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK [2] Clinical Pharmacology, The Royal Liverpool University Hospital, Liverpool, UK.
authors: M
authors: M
authors: Pirmohamed
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics*; D000077144:Clopidogrel; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D010597:Pharmacogenetics / Q000639:trends; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D012084:Renin-Angiotensin System / Q000187:drug effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine