The relative increased risk of each genetic variant is small, averaging 18% with an odds ratio varying from 2% to 90%. For CAD as well as other common polygenic disorders, multiple genetic risk variants are inherited by everyone. Those at high genetic risk

for CAD have a greater genetic risk burden due to inheritance of a greater number of common risk variants, as opposed to inheriting one or more genetic variant of high risk. In a CARDIoGRAM analysis of 23 genetic risk variants for CAD, the average number inherited per individual (case or control) was 17, varying from a minimum of 7 to a maximum of 37. Most of the genetic risk variants for CAD are located in DNA sequences that do not code for protein. This means the risk variant Inhibitors,research,lifescience,medical mediates its increased risk for CAD directly or indirectly through regulation of DNA sequences that do code for protein. All DNA genetic risk variants need only be assessed once, since one’s DNA does not change over one’s lifetime nor do genetic risk variants vary with time, meals, Inhibitors,research,lifescience,medical drugs, or gender. Pathological and Therapeutic Implications of Genetic Risk Variants for CAD A brief analysis of Table

1 indicates that only 15 of the 50 genetic risk variants are associated with conventional risk factors for CAD: seven associated Inhibitors,research,lifescience,medical with low density lipoprotein-cholesterol (LDL-C); one with high density lipoprotein (HDL); two with Inhibitors,research,lifescience,medical triglycerides; four with hypertension; and one with coronary thrombosis. The remaining 35 risk variants operate through mechanisms yet to be determined. While the hope is to ultimately use these genetic risk variants for more effective primary and secondary prevention, the VE-822 cell line immediate surprise is that many other factors contribute to the pathogenesis of atherosclerosis and CAD that are yet unknown. Research can now be directed towards these new genetic risk factors with the hope of identifying new pathways that lead to CAD. This implies a great opportunity Inhibitors,research,lifescience,medical to develop new biomarkers for

detecting early CAD as well as unique targets for novel therapy. Just as 10 of these genetic risk variants mediate their risk through lipids, it is expected that the 35 genetic risk variants of unknown function will mediate their risk through only a few pathways. Identification of these molecular pathways will provide for early detection and more effective prevention of this disease. It is self-evident SB-3CT that until we identify these pathways, we are unlikely to be comprehensive in our prevention of CAD. The identification of PCSK9 has already led to the development of new therapies for CAD as described below. Genetics Leads to New Therapy for CAD: PCSK9 Inhibition Evidence that cholesterol plays a major role in the pathogenesis of atherosclerosis has been known for more than five decades. However, one of the major observations confirming the link between cholesterol and heart disease was from human genetics.