Disease relevance of Hyperlipoproteinemia Type III

• This marked deficiency of apoE resulted in delayed uptake of chylomicron and very low density lipoprotein (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild hypertriglyceridemia, and the development of type III hyperlipoproteinemia [1].
• A variant of apolipoprotein E, denoted apo E3-Leiden, has been identified in a 41-year-old male suffering from type III hyperlipoproteinemia with xanthomatosis [2].
• Subfractionation of HDL revealed that the lipid transfer to HDL3 was significantly reduced in all patient groups while transfer to HDL2 was increased in those with dysbetalipoproteinemia and familial hypertriglyceridemia [3].
• Applied in a study in which 20 patients participated (eight patients with familial dysbetalipoproteinemia (FD), six patients with familial combined hyperlipidemia (FCH) and six controls) we found that vitamin A, no longer paralleled the apo B-48 concentrations from 9 h after a fat load, especially in the remnant fraction with Sf 15-100 [4].
• Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia [5].

High impact information on Hyperlipoproteinemia Type III

• In studies in vitro, LDL from both patients failed to bind to the LDL receptor of normal blood lymphocytes, whereas LDL from subjects with familial Type III hyperlipoproteinemia bound normally to the receptor [6].
• A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease [7].
• The same method was used to study the abnormal beta-VLDL of two type III hyperlipoproteinemia patients having markedly differing ratios of VLDL cholesterol to triglyceride (0.3 and 0.6, respectively) [8].
• Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2 [9].
• Transgenic mice were prepared that expressed a dysfunctional apo E variant, apo E (Arg-112, Cys-142), which is associated with dominant inheritance of type III hyperlipoproteinemia (type III HLP) in humans [10].

Chemical compound and disease context of Hyperlipoproteinemia Type III

• In dysbetalipoproteinemia, esterification rates were increased above normal levels, but cholesteryl ester transfer was reduced and the direction of sterol transport between the cells and plasma medium was reversed, as in the hyperbetalipoproteinemic group [11].
• Type III hyperlipoproteinemia: paradoxical hypolipidemic response to estrogen [12].
• Intravenous infusion of heparin into two subjects with type III hyperlipoproteinemia resulted in the complete removal of fraction II particles from density less than 1.006 g/ml, while fraction I particles remained at this density [13].
• The defective binding of apolipoprotein (apo) E2 to lipoprotein receptors, an underlying cause of type III hyperlipoproteinemia, results from replacement of Arg 158 with Cys, disrupting the naturally occurring salt bridge between Asp 154 and Arg 158 [14].
• Transgenic mice were produced that expressed different plasma levels (3-60 mg/dl) of human apolipoprotein (apo) E2(Arg158 --> Cys), which is associated with the recessive form of human type III hyperlipoproteinemia (HLP) [15].

Biological context of Hyperlipoproteinemia Type III

• Familial dysbetalipoproteinemia has been reported to be associated uniquely with an apolipoprotein E phenotype (E2/2) that occurs in approximately 1% of all persons [16].
• Apolipoprotein E levels are increased out of proportion to triglyceride levels in hyperlipidemic patients with familial dysbetalipoproteinemia (homozygotes for lack of apolipoprotein E-3) [17].
• The mutation was then found in 5 of 18 patients with type III hyperlipoproteinemia who had the apoE2/2 genotype (allele frequency = 13.9%; P < or = 7.4 x 10(-5)) and 6 of 22 hyperlipidemic E2 heterozygous patients with the apoE3/2 and E4/2 genotype (allele frequency = 13.6%; P = 2.2 x 10(-5)) [18].
• Especially discrimination between apoE2/E2 and apoE2/E3 genotypes is more reliable with CE than with AGE, this being of great clinical value in the diagnosis of familiary dysbetalipoproteinemia [19].
• Lovastatin therapy in familial dysbetalipoproteinemia: effects on kinetics of apolipoprotein B [20].

Anatomical context of Hyperlipoproteinemia Type III

• Adipose tissue lipoprotein lipase activity in type III hyperlipoproteinemia [21].

Gene context of Hyperlipoproteinemia Type III

• Recently, using an APOE cDNA probe, we discovered an Hpa I restriction fragment length polymorphism (RFLP) that appeared to be strongly associated with the expression of type III hyperlipoproteinemia (Klasen et al. 1987) [22].
• To investigate a pathophysiological relevance, the effect of LPL and normal apo E-3 was compared to LPL and four apo E variants, associated with type III hyperlipoproteinemia (HLP) [23].
• One of the mutations (Ser267Phe) is known to cause HTGL deficiency and is associated with type III hyperlipoproteinemia [24].
• Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene [25].
• Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia [26].

Analytical, diagnostic and therapeutic context of Hyperlipoproteinemia Type III

• The apolipoprotein E isolated from plasma of individuals with type III hyperlipoproteinemia (HLP) shows an abnormal pattern when it is examined by isoelectric focusing [27].
• Because the cholesterol-rich very low density (VLD) lipoproteins of subjects with type III hyperlipoproteinemia are distinctively enriched in apolipoprotein E, a radial immunodiffusion assay for apolipoprotein E in whole plasma was developed [28].
• In this retrospective study we report the results of treatment with clofibrate during at least 7 years in 9 patients with severe type III hyperlipoproteinemia [29].
• They also indicate that plasmapheresis using a dextran sulfate-cellulose column is very effective in the removal of abnormal lipoproteins such as beta-very low density lipoprotein and intermediate density lipoprotein in a case of familial type III hyperlipoproteinemia [30].
• With a fat restricted diet, plasma triglyceride levels abruptly fell post partum to less than 500 mg/dl, and subsequent studies revealed familial type III hyperlipoproteinemia [31].

References