Genetic factors affecting blood lipoproteins: the candidate gene approach.

Family studies have revealed that individual variations in the levels and structures of lipoproteins in the blood are due in large part to hereditary influences. Since such lipoprotein variations are strongly associated with atherosclerosis, the major cause of heart disease and stroke, the characterization of these hereditary influences provides an opportunity to better understand the genetic components contributing to the disease. Many laboratories have now taken up this challenge (reviewed in ref. 1). The problem is a difficult one, since the lipoprotein variations clearly result from a large variety of hereditary as well as environmental factors. Atherosclerosis is undoubtedly even more complex and may, like cancer, have myriad causes. In this review approaches to the problem and the results obtained to date are discussed. The most powerful strategy involves combined genetic and biochemical studies of candidate genes genes at which allelic variation is likely to affect lipoprotein phenotypes. Among such candidate genes, many of which have now been characterized, are those encoding apolipoproteins, lipoprotein receptors, and enzymes involved in lipid metabolism. This review focuses on relatively common genetic differences rather than rare mutations. Since animals provide useful models for the genetic control of lipoprotein metabolism, results from animal and human studies have been integrated.