American Journal of Epidemiology Vol. 155, No. 6 : 487-495
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health
HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW |
Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review
1 Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma, Oklahoma City, OK.
2 Pathology Department, College of Medicine, University of Oklahoma, Oklahoma City, OK.
ABSTRACT
This review examines the association between the apolipoprotein (apo) 
gene polymorphism (or its protein product (apo E)), metabolic regulation of cholesterol, and cardiovascular disease. The apo gene is located at chromosome 19q13.2. Among the variants of this gene, alleles *2, *3, and *4 constitute the common polymorphism found in most populations. Of these variants, apo *3 is the most frequent (>60%) in all populations studied. The polymorphism has functional effects on lipoprotein metabolism mediated through the hepatic binding, uptake, and catabolism of chylomicrons, chylomicron remnants, very low density lipoprotein (VLDL), and high density lipoprotein subspecies. Apo E is the primary ligand for two receptors, the low density lipoprotein (LDL) receptor (also known as the B/E receptor) found on the liver and other tissues and an apo E-specific receptor found on the liver. The coordinate interaction of these lipoprotein complexes with their receptors forms the basis for the metabolic regulation of cholesterol. Allelic variation in apo is consistently associated with plasma concentrations of total cholesterol, LDL cholesterol, and apo B (the major protein of LDL, VLDL, and chylomicrons). Apo has been studied in disorders associated with elevated cholesterol levels or lipid derangements (i.e., hyperlipoproteinemia type III, coronary heart disease, strokes, peripheral artery disease, and diabetes mellitus). The apo genotype yields poor predictive values when screening for clinically defined atherosclerosis despite positive, but modest associations with plaque and coronary heart disease outcomes. In addition to genotype-phenotype associations with vascular disease, the alleles and isoforms of apo have been related to dementias, most commonly Alzheimer's disease.
apolipoproteins E; cardiovascular diseases; epidemiology; genetics
Abbreviations: apo, apolipoprotein; CHD, coronary heart disease; CI, confidence interval; LDL, low density lipoprotein; VLDL, very low density lipoprotein
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