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Question: Which ApoE isoform is associated with hyperlipoproteinemia?

Context: ApoE2 which differs from apoE3 by the single amino acid substitution Arg158Cys located near the LDLR recognition site exhibits impaired binding to the receptor and an inability to promote clearance of TG-rich lipoprotein remnant particles; this isoform is associated with Type-III hyperlipoproteinemia.
Type III hyperlipoproteinemia (HLP), a disorder associated with a high incidence of premature cardiovascular diseases, is characterized by the accumulation of remnant lipoproteins in the plasma. The primary genetic defect in patients with type III HLP is the presence of apolipoprotein E2 (apoE2), an isoform of apoE, and accumulation of remnant lipoproteins in the plasma has been thought to be attributable to the presence of apoE2, which bind poorly to low density lipoprotein receptors, resulting in defective remnant lipoprotein clearance.
ApoE2 polymorphism is well known for its relationship to type III hyperlipoproteinemia, and the common apoE2 isoform is encoded by the R158C allele.
Reduced expression of the LDLR is believed to be a precipitating factor in the pathogenesis of type III hyperlipoproteinemia (HLP) in some humans homozygous for the apoE2 allele (APOE*2).
Overall, the 2.3-fold normal level of LDLR message in heterozygotes completely ameliorates type III HLP caused by the homozygosity for the human APOE*2 allele, normalizing their plasma lipoprotein profile.
Isoform (allele)-specific effects include the association of apoE2 with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis and the association of apoE4 with increased risk for both atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth; isoform-specific differences in cellular signaling events may also exist.
Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2.
Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoproteinemia.
ApoE has three major genetically determined isoproteins in plasma, designated apoE-2, apoE-3 and apoE-4, with homozygosity for the allele coding for apoE-2 being associated with dysbetalipoproteinemia or type III hyperlipoproteinemia (HLP).
Type III hyperlipoproteinemia typically is associated with homozygosity for apolipoprotein (apo) E2(Arg158----Cys).
ApoE is a polymorphic protein, and homozygosity for the E2 allele is associated with type III hyperlipoproteinemia.
Homozygosity for the apolipoprotein (apo) E variant apoE2(158 Arg----Cys) invariably gives rise to dysbetalipoproteinemia, and when associated with obesity or a gene for hyperlipidemia, results in type III hyperlipoproteinemia.
ApoE has three major genetically determined isoproteins in plasma, designated apoE-2, apoE-3 and apoE-4, with homozygosity for the allele coding for apoE-2 being associated with dysbetalipoproteinemia or type III hyperlipoproteinemia (HLP).
From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia.
Isoform (allele)-specific effects include the association of apoE2 with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis and the association of apoE4 with increased risk for both atherosclerosis and Alzheimers disease, impaired cognitive function, and reduced neurite outgrowth; isoform-specific differences in cellular signaling events may also exist
Whereas the association of the apo E2 isoform with primary dysbetalipoproteinemia and hyperlipoproteinemia type III is well established, the plasma- and LDL-cholesterol lowering effects of apo E2 and the phenomenon of apo E4 raising these parameters on the development of coronary heart disease is still a matter of controversial discussion.
The primary genetic defect in patients with type III HLP is the presence of apolipoprotein E2 (apoE2), an isoform of apoE, and accumulation of remnant lipoproteins in the plasma has been thought to be attributable to the presence of apoE2, which bind poorly to low density lipoprotein receptors, resulting in defective remnant lipoprotein clearance.
In the normal population, ApoE3 isoform is the most prevalent, and ApoE2 or E4 is frequently associated with hyperlipoproteinemia.
ApoE2 which differs from apoE3 by the single amino acid substitution Arg158Cys located near the LDLR recognition site exhibits impaired binding to the receptor and an inability to promote clearance of TG-rich lipoprotein remnant particles; this isoform is associated with Type-III hyperlipoproteinemia.
In the normal population apo E3 isoform is most prevalent and apo E2 or E4 is frequently associated with hyperlipoproteinemia.
From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia.
We describe a new variant of apoE, apoE-1Harrisburg, which is, in contrast to apoE-2, dominantly associated with type III HLP.
ApoE2 polymorphism is well known for its relationship to type III hyperlipoproteinemia, and the common apoE2 isoform is encoded by the R158C allele.
Type III hyperlipoproteinemia is characterized by delayed chylomicron and VLDL remnant catabolism and is associated with homozygosity for the apoE-2 allele.
The association of the E2/2 phenotype with type IV/V hyperlipoproteinemia rather than type III hyperlipoproteinemia in identical twin brothers led us to investigate the primary structure of their apoE.
ApoE2 is defective in binding and homozygosity for apoE2 is associated with type III hyperlipoproteinemia (HLP).
Homozygous carriers of apoE2 have an increased risk to develop type III hyperlipoproteinemia, whereas apoE4 is associated with elevated levels of low-density lipoprotein cholesterol.
Patients homozygous for apolipoprotein E2 are predisposed to type III hyperlipoproteinemia, and apoE2 may be protective against AD.
ApoE2 isoform, or Apolipoprotein E2 isoform