title: Clinical application of cardiovascular pharmacogenetics.
abstract: Pharmacogenetics primarily uses genetic variation to identify subgroups of patients who may respond differently to a certain medication. Since its first description, the field of pharmacogenetics has expanded to study a broad range of cardiovascular drugs and has become a mainstream research discipline. Three principle classes of pharmacogenetic markers have emerged: 1) pharmacokinetic; 2) pharmacodynamic; and 3) underlying disease mechanism. In the realm of cardiovascular pharmacogenetics, significant advances have identified markers in each class for a variety of therapeutics, some with a potential for improving patient outcomes. While ongoing clinical trials will determine if routine use of pharmacogenetic testing may be beneficial, the data today support pharmacogenetic testing for certain variants on an individualized, case-by-case basis. Our primary goal is to review the association data for the major pharmacogenetic variants associated with commonly used cardiovascular medications: antiplatelet agents, warfarin, statins, beta-blockers, diuretics, and antiarrhythmic drugs. In addition, we highlight which variants and in which contexts pharmacogenetic testing can be implemented by practicing clinicians. The pace of genetic discovery has outstripped the generation of the evidence justifying its clinical adoption. Until the evidentiary gaps are filled, however, clinicians may choose to target therapeutics to individual patients whose genetic background indicates that they stand to benefit the most from pharmacogenetic testing.
authors: Duke Institute for Genome Science & Policy, Duke University, Durham, NC 27708, USA. deepak.voora@duke.edu
authors: Deepak
authors: D
authors: Voora
authors: Geoffrey S
authors: GS
authors: Ginsburg
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000494:pharmacology; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D001057:Apolipoproteins E / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002317:Cardiovascular Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D004232:Diuretics / Q000378:metabolism / Q000494:pharmacology; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D027381:Liver-Specific Organic Anion Transporter 1; D055118:Medication Adherence; D006899:Mixed Function Oxygenases / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D064417:Vitamin K Epoxide Reductases
chemical_list: C513055:ABCB1 protein, human; C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D001057:Apolipoproteins E; D002317:Cardiovascular Agents; D004232:Diuretics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D010975:Platelet Aggregation Inhibitors; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C503999:SLCO1B1 protein, human; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D064417:Vitamin K Epoxide Reductases; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human