Apolipoproteins are proteins that have binding affinity for lipids to form packages called lipoproteins. They are responsible for transporting lipids through the lymphatic and circulatory systems. The APOE gene encodes the Apolipoprotein E protein, which is a major component of chylomicrons and VLDLs (Very Low-Density Lipoproteins). They are mainly involved in packaging and transporting cholesterol in the body. Maintaining normal levels of cholesterol is essential for the prevention of cardiovascular disease. Genetic variations in the APOE gene can influence an individual’s predisposition for developing high LDL cholesterol, Type III Hyperlipoproteinemia type III and cardiovascular disease. There are three common APOE gene variants: APOE e2, APOE e3 and APOE e4, which differ at two locations in the sequence. Different APOE alleles have different affinities for lipoproteins. APOE e2 Homozygous APOE e2 alleles are associated with lower LDL cholesterol levels, and lower incidence of coronary heart disease. However, in the presence of other environmental or genetic factors, individuals with this allele are prone to developing Type III Hyperlipoproteinemia. The APOE e2 allele has lower binding affinity for VLDL and slower cholesterol metabolism. This results in slower rate of conversion of VLDL remnants to LDL cholesterol, leading to accumulation of VLDL remnants and lower blood cholesterol. APOE e3 The APOE e3 allele is the most commonly observed allele, and is not associated with elevated LDL cholesterol or hyperlipoproteinemia type III. APOE e4 The APOE e4 allele is associated with elevated LDL cholesterol levels, which can lead to increased risk of developing atherosclerosis and cardiovascular disease. The APOE e4 allele has higher affinity for VLDL and faster metabolism, resulting in high blood cholesterol level and lower levels of remnant particles. References: Song Y, Stampfer MJ, Liu S (2004). Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease. Ann Intern Med. 141(2): 137-147.