Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein E from human serum shows a genetic polymorphism determined by two autosomal codominant alleles, Apo En and Apo Ed. Homozygosity for the gene Apo Ed (phenotype Apo E-D) results in primary dysbetalipoproteinemia, but only some individuals with this phenotype develop gross hyperlipidemia (hyperlipoproteinemia type III). Vertical transmission of dysbetalipoproteinemia represents pseudodominance due to the high frequency of the gene Apo Ed. Dysbetalipoproteinemia is already expressed in childhood. To assess the influence of other genes on the expression of hyperlipidemia in phenotype Apo E-D, comparative studies were carried out in kindreds of hypercholesterolemic (group A) and normo- or hypocholesterolemic probands with dysbetalipoproteinemia (group B). This demonstrated the occurrence of familial (non-type III) forms of hyperlipidemia in group A but not in group B kindreds. Distribution of lipoprotein phenotypes in five of the group A kindreds was consistent with the occurrence of familial combined hyperlipidemia. Apo E phenotypes and hyperlipidemia segregated independently. It is concluded that primary dysbetalipoproteinemia is a frequent monogenic variant of lipoprotein metabolism, but not a disease. Coincidence in one individual of genes for this specific dyslipoproteinemia with any of the genes for monogenic or polygenic forms of familial hyperlipidemia results in hyperlipoproteinemia type III. Hence hyperlipoproteinemia type III is caused by at least two non-allelic genes and is a polygenic disorder.
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PMID:Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III. 21 60

Apolipoprotein E polymorphism is responsible for the existence in the population of six apo E phenotypes determined by three alleles acting at a single gene locus. We have previously reported an enrichment in the epsilon 2 allele and the E2-bearing phenotypes in an unselected sample of subjects with primary hyperlipidemia consisting mainly of endogenous hypertriglyceridemia (Type IV). A study was carried out on 214 Type IV hypertriglyceridemic subjects to determine whether there was the same distribution in subjects with hyperapobetalipoproteinemia as in those without. The study showed that the relative enrichment in the epsilon 2 allele was associated only with Type IV subjects without hyperapobetalipoproteinemia. Since hyperapobetalipoproteinemia is a presumed marker for familial combined hyperlipidemia (FCHL), this finding may provide further evidence that FCHL and familial hypertriglyceridemia, both associated with a Type IV lipoprotein pattern, are truly separate disease entities.
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PMID:Apo E allele frequency in primary endogenous hypertriglyceridemia (type IV) with and without hyperapobetalipoproteinemia. 386 49

Apolipoprotein E phenotypes were determined on 417 consecutive lipid clinic patients using an isoelectric focussing technique. Of the 15 patients with phenotype E2/2, 13 (3.1%) had type III hyperlipoproteinaemia and 2 obese identical twins had type V. A further 20 patients (4.8%) had similar plasma and lipoprotein lipid levels but were E2 heterozygotes (14 E3/2 and 6 E4/2). They displayed a widened pre-beta-band almost confluent with the beta-band rather than the broad beta-band shown in classical E2/2 type III patients. In view of the similarities between these heterozygotes and the classical homozygous (E2/2) type III patients and their occurrence in the same families we suggest the nomenclature homozygous and heterozygous type III. In a subsequent comparison between 30 E2/2, 22 E3/2 and 8 E4/2 type III individuals the only significant difference in plasma and lipoprotein lipid parameters was a lower VLDL cholesterol to triglyceride ratio of 0.85 in E3/2 patients than that of 1.24 in E2/2 patients (P less than 0.01). Both homozygous and heterozygous patients showed premature ischaemic heart disease and both responded dramatically and similarly to treatment with clofibrate. These observations indicate that apo E phenotyping is worthwhile in all patients with combined hyperlipidaemia and that homozygous and heterozygous type III hyperlipoproteinaemia is not uncommon.
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PMID:Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment. 386 82

Apolipoprotein E phenotypes were determined in 361 patients with hyperlipidemia and in controls. The E2 isoform was significantly more frequent in the group of hyperlipidemics (P less than 0.0005). This was not due to a higher frequency of E-2/2 homozygotes with type III hyperlipoproteinemia, but rather to a significantly higher frequency of E2 heterozygotes (P less than 0.0005). Subgrouping of hyperlipidemics into patients with a) hypertriglyceridemia, b) hypercholesterolemia and c) mixed hyperlipidemia revealed i) that isoform E2 was significantly more frequent in patients with hypertriglyceridemia (0.001 greater than P greater than 0.005), ii) that isoform E4 was significantly more frequent in patients with hypercholesterolemia (0.01 greater than P greater than 0.005) and iii) that isoforms E2 (P less than 0.005) and E4 (0.05 greater than P greater than 0.025) were both more frequent in patients with mixed hyperlipidemia. Roughly 20% of patients with mixed hyperlipidemia had one of the rare phenotypes E-4/4, -4/2 or -2/2. We conclude that alleles epsilon 2 and epsilon 4 both contribute to the susceptibility for, and/or phenotypic expression of hyperlipidemia. Whereas the gene epsilon 2 seems to exert its influence on plasma lipoproteins by an abnormal gene product (E2) that has reduced binding activity to lipoprotein receptors, the mechanism underlying the association of the epsilon 4 gene with hyperlipidemia is presently unclear.
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PMID:Apolipoprotein E phenotypes and hyperlipidemia. 669 47

Subjects with type III hyperlipoproteinemia develop premature atherosclerosis and have hyperlipidemia due to an increase in cholesterol-rich very low density lipoproteins (VLDL) of abnormal electrophoretic mobility. Apolipoprotein E is a major protein constituent of VLDL and appears to be important for the hepatic uptake of triglyceride-rich lipoproteins. A new kindred of patients with type III hyperlipoproteinemia is described in which no plasma apolipoprotein E could be detected, consistent with the concept that type III hyperlipoproteinemia may be due to an absence or striking deficiency of apolipoprotein E.
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PMID:Type III hyperlipoproteinemia associated with apolipoprotein E deficiency. 679 20

The transfer of cholesteryl esters and apolipoprotein E has been studied between plasma HDL and chylomicrons isolated either from ascitic fluid or from the plasma of a patient with type V hyperlipoproteinemia. Whereas apolipoprotein E transfer was rapid and occurred at low temperature, cholesteryl ester transfer was suppressed at 4 degrees C. Apolipoprotein E transfer did not depend upon the presence of cholesteryl ester transfer protein and was in fact inhibited by the partially purified preparation of this protein. Apolipoprotein E transfer was not increased by reduction with dithiothreitol. The transfer of cholesteryl esters increased sharply at a chylomicron to HDL ratio of cholesteryl ester above 1/10, a value which may be of physiological significance at the peak of postprandial lipemia. At this ratio, the transfer of apolipoprotein E was minimal and increased only at ratios above 2/1. From these results, it is concluded that there is no connection between apolipoprotein E and cholesteryl ester transfer from HDL to chylomicrons. It is, therefore, proposed that whereas chylomicron apolipoprotein E is acquired rapidly and mostly in the lymphatic system, the concentration of chylomicron cholesteryl esters increases significantly and independently in the circulation.
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PMID:Cholesteryl ester and apolipoprotein E transfer between human high density lipoproteins and chylomicrons. 686 Jun 92

Apolipoprotein E isomorphs in very low density lipoproteins and apolipoprotein B of low density lipoproteins were measured in the plasma of normolipidemic subjects with xanthelasmas of the eyelids and in appropriate control groups. All patients tested in the experimental group had an apolipoprotein EII to apolipoprotein EIII ratio typical of the heterozygous state for familial dysbetalipoproteinemia, a hyperapobetalipoproteinemia, or both. Some patients had concomitant atherosclerosis. This is the first report of an increased frequency of the apolipoprotein E-ND phenotype in normolipidemic xanthelasma. This condition should not be dismissed as benign; tissue lipid deposition in the absence of hyperlipidemia might be related to the presence of lipoproteins of abnormal composition with an enhanced atherogenic potential.
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PMID:Increased Frequency of Apo E-ND phenotype and hyperapobeta-lipoproteinemia in normolipidemic subjects with xanthelasmas of the eyelids. 705 63

Apolipoprotein E (apoE)-deficient mice develop marked hyperlipidemia as well as atherosclerosis and thus are an excellent animal model for evaluating the potential for gene therapy in human genetic dyslipoproteinemias. Recombinant adenovirus containing either human apoE (rAdv.apoE) or the reporter gene luciferase (rAdv.luc) were generated and infused intravenously in apoE-deficient mice with preinfusion plasma total cholesterol of 644 +/- 149 mg/dl an cholesterol rich VLDL/IDL. After a single infusion of rAdv.apoE, plasma concentrations of human apoE ranging from 1.5 to 650 mg/dl were achieved. Adenovirus-mediated apoE replacement resulted in normalization of the lipid and lipoprotein profile with markedly decreased total cholesterol (103 +/- 18mg/dl), VLDL, IDL, and LDL, as well as increased HDL. Measurement of aortic atherosclerosis 1 mo after adenoviral infusion demonstrated a marked reduction in the mean lesion area of mice infused with rAdv.apoE (58 +/- 8 x 10(3) microns2) when compared with control mice infused with rAdv.luc (161 +/- 10 x 10(3) microns2; P < 0.0001). Thus, apoE expression for 4 wk was sufficient to markedly reduce atherosclerosis, demonstrating the feasibility of gene therapy for correction of genetic hyperlipidemias resulting in atherosclerosis. The combined use of adenovirus vectors and the apoE-deficient mouse represents a new in vivo approach that will permit rapid screening of candidate genes for the prevention of atherosclerosis.
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PMID:Apolipoprotein E deficiency in mice: gene replacement and prevention of atherosclerosis using adenovirus vectors. 765 31

Apolipoprotein E (apoE) deficiency causes severe hyperlipidemia and atherosclerosis in humans and in gene-targeted mice. Although the majority of apoE in plasma is of hepatic origin, apoE is synthesized by a variety of cell types, including macrophages. Because macrophages derive from hematopoietic cells, bone marrow transplantation was used to examine the potential of apoE synthesized by bone marrow-derived cells to correct the hyperlipidemia and atherosclerosis caused by apoE deficiency. After transplantation of bone marrow from mice with the normal apoE gene into apoE-deficient mice, apoE was detected in serum and promoted clearance of lipoproteins and normalization of serum cholesterol levels. ApoE-deficient mice given transplants of normal bone marrow showed virtually complete protection from diet-induced atherosclerosis.
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PMID:Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation. 786 32

Apolipoprotein E (apoE) has high affinity for the cell surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma chylomicron clearance, a transgenic mouse line which overexpresses apoE in the intestine was established. Immunohistochemistry demonstrated that considerable amounts of apoE were localized to mucosal cells of the intestine. In an oral retinyl palmitate challenge test, both the peak height and area under the curve in transgenic mice were less than 25% of those in controls. We speculate that the apoE molecules produced in the intestine of transgenic mice were incorporated onto newly synthesized chylomicron particles before their secretion into the plasma and thereby contributed to rapid plasma clearance of chylomicron remnants. Gene expression of apoE in the intestine would be a promising way to control postprandial hyperlipemia.
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PMID:Metabolism of chylomicron remnants in transgenic mice expressing apolipoprotein E in the intestine. 817 5


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