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

Three cases of xanthomata associated with Type II and III hyperlipidemia are presented. A review of the radiologic manifestations of these and previously reported cases revealed that tendon xanthomata are more frequent than osseous ones. Osseous involvement is reported only in Type III hyperlipidemia and should be considered in the differential diagnosis of soft-tissue masses and bone marrow replacement disorders.
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PMID:Intra- and extraosseous xanthomata associated with hyperlipidemia. 66 24

Dysbetalipoproteinaemia is a genetic disorder characterized by accumulation of lipoprotein remnant particles in the plasma, accelerated atherosclerosis, and the abnormal apoprotein E2. Uncontrolled diabetes mellitus can aggravate the hyperlipidaemia associated with this disorder, presumably by increasing triglyceride synthesis and reducing very low density lipoprotein catabolism by lipoprotein lipase. This report documents the gradual amelioration of dysbetalipoproteinaemia in uncontrolled diabetes mellitus following therapy with exogenous insulin alone. Although the beneficial effects of insulin therapy in this patient may include inhibition of triglyceride synthesis and improved triglyceride catabolism, we propose that insulin may also stimulate clearance of atherogenic remnant lipoprotein particles.
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PMID:Potential role of insulin in the clearance of remnant lipoproteins in dysbetalipoproteinaemia. 199 70

Two alleles identified by DNA restriction fragment length polymorphisms around the apo A-1/C-III and insulin genes have been shown to be associated with Type IV and V hyperlipidaemia. We have genotyped 19 patients with Type III hyperlipidaemia to establish whether this association is also found in the disorder. Our data show that these associations are not responsible for the majority of cases of Type III hyperlipidaemia, but cannot exclude the possibility that a small proportion (less than 50%) of cases of Type III are caused by interaction between these alleles and the apolipoprotein E2 phenotype.
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PMID:DNA polymorphisms flanking the apo A-1 and insulin genes and type III hyperlipidaemia. 298 7

Familial dysbetalipoproteinemia is characterized by hyperlipidemia, increases in beta-migrating, very low density lipoproteins (beta-VLDL), and homozygosity for apolipoprotein E2 (apo E2). In this study, 3 patients with familial dysbetalipoproteinemia were treated with lovastatin, and kinetics for apolipoprotein B (apo B) were determined in control and drug treatment periods. Multicompartmental analyses of apo B kinetics in VLDL and in low density lipoproteins (LDL) were carried out. Lovastatin therapy generally lowered plasma concentrations of apo B and cholesterol in VLDL and LDL. The reductions in concentrations were due mainly to a decrease in transport (production) rates for these fractions. Indeed, the fractional clearance rate (FCR) for LDL-apo B was reduced during lovastatin therapy. The decreased transport rate for VLDL-apo B and LDL-apo B could have been due to an inhibition of the synthesis of lipoproteins containing apo B. An alternate explanation is that lovastatin promoted direct removal of a rapidly-catabolized fraction of VLDL-apo B that is a precursor for longer-lived lipoproteins in the circulation; this mechanism could decrease input rates of identifiable lipoprotein species and retard their clearance because of "saturation" of LDL receptors by more rapidly removed lipoproteins. Finally, both mechanisms, i.e., decreased production and increased clearance of lipoproteins, may have contributed to the fall in VLDL-apo B and LDL-apo B concentrations during lovastatin therapy.
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PMID:Lovastatin therapy in familial dysbetalipoproteinemia: effects on kinetics of apolipoprotein B. 316 80

The fibric acid derivatives continue to have a place in the treatment of hyperlipidemia. The third generation of these drugs, including fenofibrate, appears to offer some advantages over those currently available in the United States. These drugs should be prescribed only after dietary and lifestyle changes have been offered as the preferable treatment. In severe hypertriglyceridemia, clofibrate, gemfibrozil, or fenofibrate may reduce the very low-density lipoprotein and chylomicron levels adequately. Dysbetalipoproteinemia may also be completely controlled by a combination of diet and any one of these drugs. When the low-density lipoprotein level is elevated, the newer fibric acid derivatives, such as fenofibrate, may be more effective in lowering the plasma cholesterol levels. This is true for those patients with elevated low-density lipoprotein and normal very low-density lipoprotein triglyceride levels, as well as those with elevated very low-density lipoprotein triglyceride levels. A 20 percent reduction in low-density lipoprotein cholesterol levels is expected when the triglyceride levels are not elevated. When the very low-density lipoprotein triglyceride levels are elevated, the low-density lipoprotein response is more variable, and on occasion the low-density lipoprotein cholesterol level may rise as the very low-density lipoprotein level is reduced. The average reduction in low-density lipoprotein cholesterol levels (about 6 percent) caused by fenofibrate may be greater in patients with elevated very low-density lipoprotein triglyceride levels than by other fibrates. In combination with other agents that lower low-density lipoprotein levels more specifically, such as the bile acid sequestrants and hydroxymethylglutaryl coenzyme A reductase inhibitors, fenofibrate may act to effect control of the triglycerides allowing management of those patients with disorders producing elevated very low-density lipoprotein and low-density lipoprotein levels. Extensive European experience with fenofibrate (six million patient-years) indicates that severe side effects are unlikely. However, the physician should monitor patients for skin rash, liver and renal function abnormalities, gastrointestinal dysfunction, and generalized muscle tenderness. All of these usually appear very early in the course of treatment and are reversible. Of greater concern is the possibility of an increased incidence of cholelithiasis, since the bile becomes relatively enriched in cholesterol during therapy with any fibric acid derivative.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Potential use of fenofibrate and other fibric acid derivatives in the clinic. 368 12

Lipoprotein metabolism was studied in eleven patients with Type III hyperlipoproteinaemia, one with normolipidaemic dysbetalipoproteinaemia and eight controls. Apolipoprotein B kinetics in very low density, intermediate density and low density lipoproteins (VLDL, IDL and LDL) was investigated. Fractional catabolic rates (FCRs) of VLDL-apo B and IDL-apo B were lower (P less than 0.005 and P less than 0.001) in the patients: 0.064 +/- 0.018 and 0.059 +/- 0.006 h-1 respectively, (mean +/- SEM), compared with 0.219 +/- 0.035 and 0.243 +/- 0.028 h-1. Synthetic rates (SRs) of IDL-apo B varied widely from 1.5 mg kg-1 day-1 in the subject with normolipidaemic dysbetalipoproteinaemia to 2.8-25.2 mg kg-1 day-1 in Type III. The mean time for conversion of IDL-apo B to LDL-apo B was prolonged, 18.7 h compared with 3.8 h in the controls (P less than 0.001). LDL-apo B pool size and SR were lower in the patients (P less than 0.05 for both). Two patients treated with gemfibrozil showed reduced hyperlipidaemia and decreased SR of VLDL-apo B and IDL-apo B. Dysbetalipoproteinaemia is associated with pronounced impairment of IDL and VLDL-remnant catabolism, lipoprotein levels reflecting an interaction between this defect and SR of these lipoproteins.
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PMID:Plasma apolipoprotein B metabolism in familial type III dysbetalipoproteinaemia. 392 66

Ten percent of the U.S. population has hyperlipidemia. The most commonly encountered phenotypes include Type IIa, Type IIb and Type IV. Anion-exchange resins are the drugs of choice for hypercholesterolemia, while gemfibrozil is the preferred agent for massive hypertriglyceridemia. Clofibrate is the drug of choice for the rare Type III hyperlipidemia. Successful management begins with evaluation of the total clinical picture, including genetic factors, measurement of cholesterol and triglycerides, and visual examination of the serum.
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PMID:Hyperlipidemia. 661 96

Serum very low (VLDL) and high density lipoproteins (HDL) from 17 hyperlipidemic patients and 10 normal subjects have been isolated by preparative ultracentrifugation, and the electrophoretic patterns of apolipoprotein E (apo E) isoforms in the lipoproteins have been examined by isoelectric focusing. Type III hyperlipidemia (dyslipoproteinemia) has been suggested to be a disease caused by an abnormal mutant of the apo E-3 isoform. In accordance with this, all patients with type III hyperlipidemia in the present study showed lack of apo E-3 in VLDL. However, all these patients demonstrated a protein zone corresponding to apo E-3 in their HDL fraction. Patients with other types of hyperlipidemia or normal subjects who showed an apo E-4 variant in VLDL had an HDL that lacked apo E-4. The results support the hypothesis that type III hyperlipidemia is due to an abnormal composition of the VLDL particles rather than a result of an abnormal mutant of apo E-3.
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PMID:Distribution of apolipoprotein E isoforms between very low and high density lipoproteins of normal subjects and hyperlipidemic patients with special reference to type III hyperlipidemia. 670 90

Intraosseous xanthoma associated with hyperlipoproteinemia, a rare disorder, was observed in the entire distal femur of a 52-year-old man. Initial radiographs suggested a primary bone neoplasm; however, an open biopsy established a diagnosis of intraosseous xanthoma. Histologically, the lesion was characterized by replacement of normal bone and marrow with xanthoma cells and extracellular cholesterol clefts. The hyperlipidemia was classified as Type III hyperlipoproteinemia and was successfully controlled by dietary lipid restriction alone. The disability was effectively treated and ambulation was possible with the aid of a cane.
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PMID:Intraosseous xanthoma associated with hyperlipoproteinemia. A case report. 674 21


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