Genetics of lipoprotein disorders

The study of lipoprotein metabolism has led to major breakthroughs in the fields of cellular physiology, molecular genetics, and protein chemistry. These advances in basic science are reflected in medicine in the form of improved diagnostic methods and better therapeutic tools. Perhaps the greatest benefit is the improved ability to identify at an early stage patients who are at high risk for atherosclerosis, providing clinicians the opportunity to proceed swiftly with intensive lipid-lowering therapy for the prevention of cardiovascular complications. Recent clinical trials have shown that such an approach is not only cost-effective but saves lives while improving the quality of life. They also emphasize the important role physicians can have in prevention. More than half of patients with premature CAD have a familial form of dyslipoproteinemia. This review of the genetics of atherogenic lipoprotein disorders underscores the importance of identifying major genetic defects. It also stresses the need to take into account multifactorial etiologies and clustering of risk factors, as well as gene-gene and gene-environment interactions in assessing the atherogenic potential of a lipid transport disorder. Table 2 summarizes the key points in the diagnosis, clinical implications, and treatment of the major inherited atherogenic dyslipidemias.