Pharmacogenetics of multigenic disease: heart disease as an example

Abstract

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.