Apolipoprotein E (apoE) is a lipid-protein complex that plays a role in the pathogenesis of heart disease. Apo E is a protein constituent of very-low-density lipoprotein (VLDL) and chylomicrons. It is believed to mediate clearing of these lipoproteins from the circulation through specific VLDL binding to cell surface receptors, and thus it plays an important role in plasma lipid metabolism. The apoE gene is polymorphic; that is, the DNA base sequence varies slightly so that the apoE proteins produced differ from each other in just one amino acid. This substitution can lead to considerable differences in activity. The three common apoE proteins -- apoE2, apoE3, and apoE4 -- are coded for by three common genes (alleles) designated e2, e3, and e4. According to biochemists Van Bockxmeer and Mamotte, at a popula-tion level the most significant determinant of plasma lipoprotein levels found to date is polymorphism in the apoE gene.
ApoE2 has a reduced affinity for the cellular receptor, so e2/e2 carriers (homozygotes) have elevated lipids in the blood, and in 5% of cases this manifests itself as type III hyperlipidemia. The e4 allele is associated with higher total and LDL cholesterol levels. Certain populations with a high incidence of CAD (e.g., Finns) have been shown to have high serum cholesterol levels and an increased frequency of e4, while populations with a low incidence of CAD and low cholesterol levels (e.g., Orientals) have a low frequency of e4. A lower e4 frequency has been reported in octogenarians, suggesting that individuals who are free of the e4 allele are the ones who survive long enough to become octogenarians.
source:Wenham PR et al. Atherosclerosis.
ApoE2 has a reduced affinity for the cellular receptor, so e2/e2 carriers (homozygotes) have elevated lipids in the blood, and in 5% of cases this manifests itself as type III hyperlipidemia. The e4 allele is associated with higher total and LDL cholesterol levels. Certain populations with a high incidence of CAD (e.g., Finns) have been shown to have high serum cholesterol levels and an increased frequency of e4, while populations with a low incidence of CAD and low cholesterol levels (e.g., Orientals) have a low frequency of e4. A lower e4 frequency has been reported in octogenarians, suggesting that individuals who are free of the e4 allele are the ones who survive long enough to become octogenarians.
source:Wenham PR et al. Atherosclerosis.
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