ABSTRACT
Hypercholesterolemia has long been recognized as a major risk factor for atherosclerosis and cardiovascular diseases (reviewed in Steinberg[1]). Individuals in the human population exhibit a large range of serum cholesterol levels as a result of differences in several factors, including absorption of cholesterol from the diet, lipoprotein production and catabolism, and synthesis and excretion of cholesterol in the form of bile acids. An example of an extreme individual variation in regulation of cholesterol levels is the “Egg Man” described by Kern.[2] This 88 year old man habitually ate 25 eggs a day, thus consuming more than 20× the recommended amount of cholesterol, yet maintained normal blood cholesterol levels and had no clinical evidence of atherosclerosis. This appeared to be explained by physiological compensatory mechanisms, including reduced absorption of dietary cholesterol in the intestine, and increased conversion of cholesterol to bile acids for elimination. This case illustrates that the study of individuals who exhibit aberrant responses to dietary cholesterol intake may provide insight into the metabolic processes involved in cholesterol homeostasis. 196With the advent of tools such as DNA microarrays, the study of genetic variation becomes even more valuable, as the basis for individual differences can be assessed at the molecular level.
