title: Pharmacogenetics and cardiovascular disease--implications for personalized medicine.
abstract: The past decade has seen tremendous advances in our understanding of the genetic factors influencing response to a variety of drugs, including those targeted at treatment of cardiovascular diseases. In the case of clopidogrel, warfarin, and statins, the literature has become sufficiently strong that guidelines are now available describing the use of genetic information to guide treatment with these therapies, and some health centers are using this information in the care of their patients. There are many challenges in moving from research data to translation to practice; we discuss some of these barriers and the approaches some health systems are taking to overcome them. The body of literature that has led to the clinical implementation of CYP2C19 genotyping for clopidogrel, VKORC1, CYP2C9; and CYP4F2 for warfarin; and SLCO1B1 for statins is comprehensively described. We also provide clarity for other genes that have been extensively studied relative to these drugs, but for which the data are conflicting. Finally, we comment briefly on pharmacogenetics of other cardiovascular drugs and highlight β-blockers as the drug class with strong data that has not yet seen clinical implementation. It is anticipated that genetic information will increasingly be available on patients, and it is important to identify those examples where the evidence is sufficiently robust and predictive to use genetic information to guide clinical decisions. The review herein provides several examples of the accumulation of evidence and eventual clinical translation in cardiovascular pharmacogenetics.
authors.affiliation: Center for Pharmacogenomics, Department of Pharmacotherapy and Translational Research, University of Florida, Box 100486, Gainesville, FL 32610-0486, USA. johnson@cop.ufl.edu
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Larisa H
authors.initials: LH
authors.lastname: Cavallari
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation / Q000235:genetics; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D027381:Liver-Specific Organic Anion Transporter 1; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D057285:Precision Medicine; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D002317:Cardiovascular Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D010975:Platelet Aggregation Inhibitors; C503999:SLCO1B1 protein, human; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D013988:Ticlopidine