Pharmacogenetics of multigenic disease: heart disease as an example.
We now have a greater understanding of the workings of the human genome as well as a wide assortment of pharmacological and mechanical therapies that clearly improve mortality and quality of life for our patients with cardiovascular disease, but these areas of therapeutics and genomics have essentially advanced independently with little interaction up until recently. Pharmacogenetics is the study of the effect of a medication as it relates to single or defined sets of genes. A major goal will be to integrate the two so that true personalized therapy can be delivered. This review explores the clinical implications of the complex interactions in multigenic disease and pharmacology with examples of atherosclerosis and heart failure. The therapies of today are the direct result of understanding the epidemiological, molecular and genetic basis of cardiovascular disease with the application to clinical practice. The complexity of multigenic disease and the promise of pharmacogenetics will require that we improve on the methods of drug evaluation and this includes the need for new statistical methods, bioinformatics, and novel clinical trial design with sufficient power to detect differences in therapy. There must be a continued effort to apply biological and mechanistic plausibility in understanding disease and pharmacology but openness to new ideas and concepts, especially in understanding the workings of the genome.
Cooke
Glen E
GE
Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, 235 DHLRI, 473 W. 12th Ave., Columbus, 43210-1252, USA. glen.cooke@osumc.edu
D016824:Antigens, Human Platelet / Q000235:genetics; D000975:Antioxidants / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000235:genetics* / Q000517:prevention & control; D015195:Drug Design; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D006331:Heart Diseases / Q000188:drug therapy / Q000235:genetics* / Q000517:prevention & control; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D015607:Stents / Q000009:adverse effects; D013923:Thromboembolism / Q000235:genetics; D014665:Vasodilator Agents / Q000627:therapeutic use
D016824:Antigens, Human Platelet; D000975:Antioxidants; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; C083451:human platelet antigen 1b; D007703:Peptidyl-Dipeptidase A