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CARDIOVASCULAR GENOMIC MEDICINE

Future Use of Genomics in Coronary Artery Disease

Samir B. Damani, MD^_* and Eric J. Topol, MD, FACC^_*,,_*

^_* Division of Cardiovascular Diseases, Scripps Clinic, La Jolla, California
Scripps Genomic Medicine, Scripps Health, and the Scripps Research Institute, La Jolla, California.

Manuscript received May 3, 2007; revised manuscript received June 29, 2007, accepted July 30, 2007.

^_* Reprint requests and correspondence: Dr. Eric J. Topol, Scripps Genomic Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM—275, La Jolla, California 92037. (Email: etopol{at}scripps.edu).

Coronary artery disease (CAD) remains the number one cause of death in industrialized countries despite our collective efforts to minimize attributable risk from known contributors to CAD such as hypertension, dyslipidemia, and smoking. In addition, clinical trials have consistently demonstrated a family history of coronary disease to be predictive for future cardiovascular events beyond that which would be explained by traditional risk factors. These findings support and have prompted widespread investigation into the genomic basis of CAD and myocardial infarction (MI). Recent advances in genotyping technology have allowed for easier identification and confirmation of susceptibility genes for complex traits across different cohorts via increased power of studies stemming from faster accrual of cases and control subjects and more precise genetic mapping. These technological advances have resulted in defining the genes contributing to a substantial or even majority of population-attributable risk for type 2 diabetes and age-related macular degeneration (AMD) cases. Similar progress in repli-cating novel susceptibility genes for CAD and specifically MI is now rapidly occurring, with a recent gene marker on chromosome 9p21 representing a highly significant and common variant susceptibility factor. With improved resequencing technology and better phenotypic characterization of our CAD cases and control subjects, we should achieve successes in gene identification and confirmation similar to diabetes and AMD, thereby allowing us to better quantify CAD risk earlier in life and institute more effective therapy reducing the individual propensity to develop CAD.

Abbreviations and Acronyms   AMD = age-related macular degeneration   apo = apolipoprotein   CAD = coronary artery disease   CFH = complement factor H   DM = diabetes mellitus   FLAP = 5-lipoxygenase activating protein   LDL = low-density lipoprotein   LTA = lymphotoxin-alpha gene   LTA4H = leukotriene A4 hydrolase   MEF2A = myocyte enhancer factor 2a   MI = myocardial infarction   RR = relative risk   SNP = single nucleotide polymorphism   TSP = thrombospondin

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