Cardiovascular pharmacogenomics: current status, future prospects.
Pharmacogenomics is a field dedicated to exploring the contribution of genetics to interindividual variability in drug response. A goal of cardiovascular pharmacogenomics is to guide cardiovascular drug development and selection so as to optimize therapeutic benefit and minimize the potential for toxicity. Genetic-based differences in drug metabolism have long been recognized but just now are on the verge of wider clinical application. Differences in efficacy of cardiovascular drugs (independent of drug concentration) based on common genetic variations (polymorphisms) only recently have begun to be explored, but the potential for clinical application appears promising. Examples are presented of important pharmacodynamic effects of genetic variants on several drugs, including those in antiarrhythmic, reninangiotensin, beta-blocker, lipid-lowering, and antithrombotic classes. Principles of pharmacogenomics applied to drug metabolism are discussed that are relevant to drug development and clinical use, and examples are given for CYP450 phase I enzymes, phase II enzymes, and drug transporters. Challenges in establishing true pharmacogenetic associations are discussed, and current and future clinical potential is summarized. Rapid research progress and initial clinical applications with pharmacogenomics are foreseen in the near future.
Anderson
Jeffrey L
JL
Intermountain Heart Collaborative Research Group, LDS Hospital Cardiovascular Department, and University of Utah School of Medicine, Salt Lake City, Utah 84143, USA.
Carlquist
John F
JF
Horne
Benjamin D
BD
Muhlestein
Joseph B
JB
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D010597:Pharmacogenetics / Q000639:trends; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002352:Carrier Proteins; D004232:Diuretics; D005343:Fibrinolytic Agents; D000960:Hypolipidemic Agents; D003577:Cytochrome P-450 Enzyme System