|Tsai, Michael -|
|Ordovas, Jose -|
Submitted to: Clinical Chemistry
Publication Type: Review Article
Publication Acceptance Date: April 30, 2009
Publication Date: July 1, 2009
Citation: Tsai, M.Y., Ordovas, J. 2009. Genetic APOC3 mutation, serum triglyceride concentrations, and coronary heart disease. Clinical Chemistry. 55(7):1274-1276. Technical Abstract: Recent decades have witnessed an increased awareness of the importance of lowering triglyceride concentrations in conjunction with lowering LDL cholesterol (LDL-C) to achieve optimal reduction of the risk for coronary heart disease (CHD). Historically, LDL-C was the only target of pharmacologic therapy in CHD prevention. Thus the first Adult Treatment Panel (ATP I) of the National Cholesterol Education Program published in 1988 used only LDL-C cutoffs as guidelines. Since then, there have been incremental changes with regard to the importance of lowering triglyceride concentrations in addition to LDL-C. In part, the increased recognition of the importance of lowering triglycerides has been a result of increased recognition of the metabolic syndrome (MS). A Genome Wide Association Study (GWAS) led to the discovery of a single nucleotide polymorphism (SNP), rs10892151, which is in linkage disequilibrium with a loss-of-function mutation in APOC3 that results in a premature stop-codon that results in the complete lack of production of apoC-III peptide. Thus carriers of this loss-of-function mutation have half the apoC-III protein concentrations, and they have reduced fasting and postprandial triglyceride concentrations, which is in agreement with the well-known function of apoC-III as an inhibitor of lipoprotein lipase. Moreover, apoC-III may activate vascular endothelial cells through increased expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Most of the therapies used in lowering triglycerides, such as niacin, fish oil, and fibrates, are also associated with a decrease in APOC3 expression. More research on the reduction of triglycerides, either singly or in combination with reduction of LDL-C, may contribute to improved clinical outcome in both primary and secondary prevention of CHD in the future.