Document Detail


Emerging genomic applications in coronary artery disease.
MedLine Citation:
PMID:  21596318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Over the last 4 years, an unprecedented number of studies illuminating the genomic underpinnings of common "polygenic" diseases including coronary artery disease have been published. Notably, these studies have established numerous deoxyribonucleic acid (DNA) variants within or near chromosome 9p21.3, the LPA, CXADR, and APOE genes, to name a few, as key coronary artery disease and sudden cardiac death susceptibility markers. Most importantly, many of these DNA variants confer over a 2-fold increase in risk for coronary artery disease, myocardial infarction, and ventricular fibrillation. Additionally, loss-of-function variants in the hepatic cytochrome 2C19 system have now been found to be the predominant genetic mediators of clopidogrel antiplatelet response, with variant carriers having a >3-fold increase in risk for stent thrombosis. In the near future, many additional rare polymorphisms, structural variants, and tissue-specific epigenetic features of the human genome including DNA methylation, histone modifications, and chromatin state will emerge as significant contributors to disease pathogenesis and drug response. In aggregate, these findings will have the potential to radically change the practice of cardiovascular medicine. However, only the individual clinician can ultimately enable the translation of these important discoveries to systematic implementation in clinical practice.
Authors:
Samir B Damani; Eric J Topol
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  JACC. Cardiovascular interventions     Volume:  4     ISSN:  1876-7605     ISO Abbreviation:  JACC Cardiovasc Interv     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-20     Completed Date:  2011-09-09     Revised Date:  2012-08-29    
Medline Journal Info:
Nlm Unique ID:  101467004     Medline TA:  JACC Cardiovasc Interv     Country:  United States    
Other Details:
Languages:  eng     Pagination:  473-82     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Division of Cardiovascular Diseases, Scripps Clinic, Scripps Translational Science Institute and the Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins E / genetics
Aryl Hydrocarbon Hydroxylases / genetics,  metabolism
Coronary Artery Disease / genetics*
Gene Expression Profiling
Genetic Predisposition to Disease
Genomics* / methods
Humans
Individualized Medicine
Lipoprotein(a) / genetics
Pharmacogenetics
Phenotype
Platelet Aggregation Inhibitors / pharmacokinetics
Polymorphism, Genetic
Risk Assessment
Risk Factors
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Lipoprotein(a); 0/Platelet Aggregation Inhibitors; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C19 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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