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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.
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PMID:Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. 231 Apr 29

Cholesterol estimations were performed on blood collected postmortem from a group of subjects coming to autopsy and showing that they had had a high risk for hypercholesterolaemia, and from an unselected group of subjects dying in hospital. Subjects from the first group had apparently been healthy, aged less than 45 years, had had no known risk factors for hyperlipidaemia, and showed extensive coronary artery atheroma (stenosis greater than 50% by diameter). Eleven cases from 485 consecutive autopsies fulfilled these criteria; three showed considerable hypercholesterolaemia (11.2, 11.8, and 21.6 mmol/L). Family studies confirmed the diagnosis of familial hypercholesterolaemia in one case; the other two remain unproven. Cholesterol measurement by cholesterol oxidase and quinoneimine dye production is subject to interference by haemolysis; provided that serum haemoglobin is less than 200 mg/dl, the cholesterol underestimate is less than 5%. The decline in serum cholesterol in the group of unselected subjects was 1.7 (0.3-4.9) mmol/L, 50.4 (28-84) h postmortem. Results are means and ranges for seven subjects. Measurement of cholesterol in serum obtained postmortem (provided that the sample is not grossly haemolysed) is a valid approximation of antemortem levels: this measurement should be made when autopsy reveals evidence of premature coronary heart disease. If hypercholesterolaemia is discovered, the diagnosis of familial hypercholesterolaemia, a common genetic disorder inherited in an autosomal dominant fashion, should be considered and appropriate family studies instituted.
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PMID:Incidence of familial hypercholesterolaemia in premature deaths due to coronary heart disease. 343 46

Although analysis of lipoprotein phenotypes is widely used to diagnose and classify the familial hyperlipidemias, an evaluation of this system as a method for genetic classification has hitherto not been published. The present study of 156 genetically defined survivors of myocardial infarction was therefore designed to examine the relationship between lipoprotein phenotypes and genetic lipid disorders. The lipoprotein phenotypes of each survivor was determined primarily by measurement of his plasma triglyceride and low density lipoprotein (LDL)-cholesterol concentrations; his genetic disorder was identified by analysis of whole plasma cholesterol and triglyceride levels in relatives. The mean levels of LDL-cholesterol discriminated statistically among the three monogenic lipid disorders; it was highest in survivors with familial hypercholesterolemia (261+/-61 mg/100 ml [mean +/-SD]); intermediate in those with familial combined hyperlipidemia (197+/-50); and lowest in those with familial hypertriglyceridemia (155+/-36) (P < 0.005 among the three groups). However, on an individual basis no lipoprotein pattern proved to be specific for any particular genetic lipid disorder; conversely, no genetic disorder was specified by a single lipoprotein pattern. This lack of correlation occurred for the following reasons: (a) individual LDL-cholesterol levels frequently overlapped between disorders; (b) in many instances a small quantitative change in the level of either LDL-cholesterol or whole plasma triglyceride caused qualitative differences in lipoprotein phenotypes, especially in individuals with familial combined hyperlipidemia, who showed variable expression (types IIa, IIb, IV, or V); (c) lipoprotein phenotypes failed to distinguish among monogenic, polygenic, and sporadic forms of hyperlipidemia; (d) clofibrate treatment of some survivors with genetic forms of hyperlipidemia caused their levels of triglyceride and LDL-cholesterol to fall below the 95th percentile, thus resulting in a normal phenotype; and (e) beta-migrating very low density lipoproteins (beta-VLDL), previously considered a specific marker for the type III hyperlipidemic disorder, was identified in several survivors with different lipoprotein characteristics and familial lipid distributions. These studies indicate that lipoprotein phenotypes are not qualitative markers in the genetic sense but instead are quantitative parameters which may vary among different individuals with the same genetic lipid disorder. It would therefore seem likely that a genetic classification of the individual hyperlipidemic patient with coronary heart disease made from a quantitative analysis of lipid levels in his relatives may provide a more meaningful approach than determination of lipoprotein phenotypes.
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PMID:Hyperlipidemia in coronary heart disease. 3. Evaluation of lipoprotein phenotypes of 156 genetically defined survivors of myocardial infarction. 435 58

The aim was to identify genetic determinants for the development of hyperlipidemia and/or atherosclerosis. The present set of studies demonstrates for the first time the clinical expression (phenotype) of a newly discovered monogenic disorder named Familial Defective Apolipoprotein B-100 (FDB). FDB is caused by a G to A mutation in the binding protein (apolipoprotein B-100) for the cholesterol-rich low density lipoprotein (LDL), such that the affinity of LDL to the LDL receptor is severely reduced. In all 135 individuals with FDB from 56 families and 8 different countries, including Denmark, are described. On average, the effect of the FDB mutation was to increase plasma and LDL cholesterol in both men and women by about 3 mmol/l; at age 55 the average plasma cholesterol of men and women with FDB was 9.4 mmol/l and 8.9 mmol/l, respectively. A sharp rise in frequency of coronary artery disease as a function of age in both FDB males and females was comparable to that found in Familial Hypercholesterolemia (FH). At the age of 60, about 70% of both men and women with FDB had coronary artery disease; at the same age approximately 40% had tendon xanthomas, and 35% had arcus corneae, irrespective of gender. Surprisingly, the frequencies of arcus corneae were not strikingly higher than those found in the general population sample from the Copenhagen City Heart Study. Only few patients with FDB had xanthelasmas. Finally, the frequency of this mutation was estimated at 1/500-1/700 in the general population, which is equivalent to that of clinical FH. All in all the results suggest FDB to be a severe genetic disorder with early penetrance, associated with substantial elevations in plasma and LDL cholesterol and with an increased frequency of premature coronary artery disease and of tendon xanthomas. For comparison, a number of common polymorphisms in the 5'-flanking region of the insulin gene, in the apoB gene and in the apoAI-CIII-AIV gene cluster, associated with minor effects on hyperlipidemia and/or cardiovascular disease are also examined.
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PMID:Rare and common mutations in hyperlipidemia and atherosclerosis. With special reference to familial defective apolipoprotein B-100. 765 81

Apo C-II has a central role in triglyceride metabolism as a cofactor for lipoprotein lipase (LPL), the enzyme that catalyzes the hydrolysis of triglycerides on plasma lipoproteins. Apo C-II deficiency is a rare genetic disorder that is inherited as an autosomal recessive trait. Patients with this syndrome have marked alterations of triglyceride metabolism which include elevated fasting triglycerides, chylomicrons, and VLDL. Clinical features also include lipemia retinalis, eruptive xanthomas, and an increased incidence of pancreatitis. The initial description of the first patient with apo C-II deficiency by Breckenridge et al. established the important role of apo C-II as a cofactor for LPL. Since then, many kindreds with apo C-II deficiency have been described and the underlying molecular defect characterized.
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PMID:[Apolipoprotein C-II deficiency]. 785 17

The finding of multiple lipomas, or lipomatosis, can be a marker for several clinical or familial syndromes. Familial multiple lipomatosis is a benign hereditary disorder of adipose regulation associated with hyperlipidemia. Multiple symmetric lipomatosis involves the local infiltration of adipose tissue of the neck, upper torso and mediastinum. This condition is often found in alcoholics and has been associated with diabetes mellitus. An afflicted patient's family history is important both to reveal occult pathology and to help determine the disease's prevalence in the population. In this article, we report the case of a patient with sporadic multiple lipomatosis and provide a brief review of the literature.
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PMID:Sporadic multiple lipomatosis: a case report and review of the literature. 800 72

Hyperlipidemia is first detected by an increase in the plasma concentrations of cholesterol and/or triglycerides, and implies an abnormality of plasma lipoprotein metabolism. Disorders of lipoprotein metabolism are often classified specifically according to the lipoprotein affected. The WHO classification of lipoprotein phenotypes is a useful means of showing which lipoproteins are present in excess in individual hyperlipidemic patients. Hyperlipoproteinemia can be secondary to other well-known diseases that affect plasma lipoprotein metabolism, for example, diabetes mellitus, hypothyroidism or nephrotic syndrome. When such diseases are excluded, the hyperlipoproteinemia is defined as primary hyperlipoproteinemia. Many primary hyperlipoproteinemias have a genetic basis and the underlying molecular defect has been clarified in some genetic disorders. Hyperlipoproteinemia is considered to be one of the major risk factors for atherosclerosis and the development of atherosclerosis depends on the type of hyperlipoproteinemia. In this sense, familial hypercholesterolemia is a clinically important primary hyperlipoproteinemia because of its high risk of ischemic heart disease and its high prevalence in a normal population (1/500). It is necessary to make an exact diagnosis of specific genetic disorder, if possible, to provide prognostic and therapeutic information.
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PMID:[Primary hyperlipoproteinemia]. 841 90

Hyperlipidemia is one of the risk factors for coronary atherosclerosis and the establishment of its simple etiological diagnosis is crucial. Hyperlipidemia can be classified into primary and secondary hyperlipidemia. Primary hyperlipidemia includes familial lipoprotein lipase (LPL) deficiency, familial hypercholesterolemia (FH), familial type III hyperlipidemia, and familial combined hyperlipidemia. Many genetic mutations have been identified in patients with familial LPL deficiency and FH. An ELISA kit has been established to determine LPL mass levels, using monoclonal antibodies against LPL. FH is a deficiency of LDL receptor and is characterized by marked hypercholesterolemia and Achilles tendon xanthomas. It can be diagnosed by an LDL receptor assay, using 125I-LDL in skin fibroblasts. However, the diagnosis can be made easily by measuring the uptake of DiI-LDL by peripheral lymphocytes. Familial type III hyperlipidemia is a genetic disorder characterized by the presence of a broad beta pattern in lipoprotein electrophoresis and is based upon the abnormality of apo E isoform (apo E2/2). Apo E4 has been shown to be associated with late-onset Alzheimer's disease. Cholesteryl ester transfer protein (CETP) deficiency is characterized by a marked hyperalphalipoproteinemia and various abnormalities in the size and composition of LDL and HDL. Two common mutations in the CETP deficiency have been identified; an intron 14 splicing defect and D442: G missense mutation. These mutations account for at least one half of hyper-HDL-cholesterolemia in the Japanese. We have recently identified an area (Omagari City, Akita) where the frequency of heterozygotes for the intron 14 splicing defect is approximately 28% of the general population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Progress in the diagnosis of endocrine and metabolic disorders: hyperlipidemia]. 855 75

Sitosterolemia is a genetic disorder characterized by sitosterol accumulation in plasma and clinically accelerated atherosclerosis. Under a condition of metabolic control with a 30% fat, low-sitosterol diet, we compared the effects of monotherapy and dual-drug treatment with lovastatin and cholestyramine on plasma sterol parameters and endogenous cholesterol synthesis in a homozygous sitosterolemic patient with concomitant heterozygous familial hypercholesterolemia (FH), her obligate heterozygous father, and hyperlipidemic control subjects. We found that for both the sitosterolemic homozygote and heterozygote, cholestyramine plus lovastatin dual therapy proved not to be superior to either drug treatment alone. In the homozygous patient, cholestyramine accounted for the decrease of plasma sterol (ie, lovastatin was ineffective), whereas in the heterozygote, lovastatin represented the margin of difference (ie, low-dose cholestyramine was relatively ineffective). Thus, the best treatment option for this homozygote child and her heterozygote father appears to be monotherapy with cholestyramine and lovastatin, respectively. Stimulation by bile acid malabsorption produced a dramatic decrease of plasma sterols in the homozygote, without increasing endogenous cholesterol synthesis, but this therapy was ineffective in the heterozygote. Decreasing endogenous cholesterol synthesis with lovastatin was effective in the heterozygote, but ineffective in the homozygote. In suspected sitosterolemia, a poor sterol response to lovastatin and a dramatic response to cholestyramine may differentiate homozygous from heterozygous and other familial forms of hyperlipidemia.
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PMID:Sitosterolemia: opposing effects of cholestyramine and lovastatin on plasma sterol levels in a homozygous girl and her heterozygous father. 863 39


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