Genetic markers for coronary artery disease.

1. Linnea M. Baudhuin, PhD, DABMG[⇑][1] 1. is assistant professor of laboratory medicine, Mayo Clinic, Jacksonville, FL 1. Address for correspondence: Linnea M. Baudhuin, PhD, DABMG, Assistant Professor of Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, (507) 284-2511, (507) 266-4176 (fax), baudhuin.linnea{at}mayo.edu. Upon completion of this activity, participants should be able to: 1. Compare linkage studies with association studies and recognize aspects regarding the utility and limitations of these studies in identifying markers associated with complex disease. 2. Describe genome wide association studies and their advantages and disadvantages for identifying genetic markers. 3. Discuss various aspects regarding the 9p21 risk allele, its association to CAD, and its potential as a clinical marker for CAD. 4. Describe microRNAs and their potential utility as CAD markers. 5. Discuss aspects of genetic markers that would lend to their ability to enter the clinical realm as risk markers for complex disease. The hereditary component of coronary artery disease (CAD) is widely recognized. However, identifying clinically useful genetic markers for a complex disease like CAD has been challenging. Linkage-based and association-based genetic studies have pointed to some interesting findings, but many of these studies have lacked reproducibility or statistical significance. Recently, genome-wide association (GWA) and microRNA discoveries have uncovered some potentially promising new markers for CAD. The current status of genetic markers for CAD and their utility in the clinical arena are summarized here. Coronary artery disease (CAD) is a multifactorial disease that can be influenced by a multitude of environmental and heritable risk factors. While there are many traditional and novel analyte risk markers associated with CAD, a large gap for CAD risk prediction remains. Epidemiological evidence points to an approximate 50% genetic susceptibility to CAD. Many different genetic associations with CAD have been identified through family and population-based analyses, and genetic risk markers may be important for better defining individuals at risk for CAD and CV events. Some potentially promising and interesting markers produced from such studies are highlighted here. Linkage Analysis and CAD Linkage analyses are family-based studies investigating genetic variants that segregate with disease in affected vs. non-affected family members. Multiple linkage studies have been performed in CAD cases, invest-tigating the occurrence of myocardial infarction (MI) or subclinical atherosclerosis.1 While several loci of interest have been identified through linkage studies, the majority of them have not been replicated or directly implicated in CAD. One gene that was identified… Upon completion of this activity, participants should be able to: 1. Compare linkage studies with association studies and recognize aspects regarding the utility and limitations of these studies in identifying markers associated with complex disease. 2. Describe genome wide association studies and their advantages and disadvantages for identifying genetic markers. 3. Discuss various aspects regarding the 9p21 risk allele, its association to CAD, and its potential as a clinical marker for CAD. 4. Describe microRNAs and their potential utility as CAD markers. 5. Discuss aspects of genetic markers that would lend to their ability to enter the clinical realm as risk markers for complex disease. [1]: #corresp-1