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CARDIOVASCULAR GENOMIC MEDICINE

Genomics and Cardiovascular Drug Development

Andrew S. Plump, MD, PhD^_*,_* and Pek Yee Lum, PhD

^_* Cardiovascular Diseases, Merck Research Laboratories, Rahway, New Jersey
Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co., Inc., Seattle, Washington

Manuscript received August 4, 2008; revised manuscript received November 20, 2008, accepted November 24, 2008.

^_* Reprint requests and correspondence: Dr. Andrew S. Plump, Cardiovascular Diseases, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, New Jersey 07065 (Email: andrew_plump{at}merck.com).

In the last half century, phenomenal advances have been made in understanding the pathophysiology of cardiovascular disease and in developing therapies to reduce cardiovascular risk. Nevertheless, cardiovascular disease remains the leading cause of death and morbidity in the industrialized world, with rapidly rising prevalence in developing countries, accounting for 30% of all deaths worldwide. Since the initial availability of statin drugs in 1987, few novel cardiovascular therapies have emerged. Whereas statins reduce the mortality and morbidity from atherosclerotic heart disease by 30%, the staggering 70% residual cardiovascular risk underscores the persistent need for novel therapies. Substantial advances in genomic research offer promise to greatly facilitate cardiovascular drug development. Over the past decade, often termed "the genomics revolution," such advancements as the emergence of genome-wide genotyping in humans, the industrialization of messenger ribonucleic acid expression profiling, and the maturation of proteomic and metabolomic methodologies have been made. In addition, the advancement of informatics to allow the intersection of multiple complex datasets has led to the field of systems biology. Genomic approaches are already being utilized to drive novel compound pipelines by helping with the identification and validation of novel targets. In the future, the study of genomics is expected to support biomarker discovery and development and the identification of responder patient segments. The focus of the present review is the application of genomics to the development of novel atherosclerosis therapies.

Key Words: biomarkers • cardiovascular disease • genomics • systems biology • target validation

Abbreviations and Acronyms   apo = apolipoprotein   CAD = coronary artery disease   CHF = congestive heart failure   CRP = C-reactive protein   CV = cardiovascular   CVD = cardiovascular disease   DM = diabetes mellitus   DNA = deoxyribonucleic acid   FH = familial hypercholesterolemia   GWAS = genome-wide association study   HDL = high-density lipoprotein   HDL-C = high-density lipoprotein cholesterol   LDL = low-density lipoprotein   LDL-C = low-density lipoprotein cholesterol   MI = myocardial infarction   RNA = ribonucleic acid   SNP = single nucleotide polymorphism

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J. Am. Coll. Cardiol. 2009 53: A24. [Full Text] [PDF]