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)

A protein band having the same migration as apolipoprotein (apo) B-48 was observed by SDS electrophoresis in the plasma very low density lipoprotein (VLDL) from 14 Type IV and three Type III hyperlipoproteinemic subjects and from six normal fasting subjects. The VLDL from five Type IV, three Type III, and one normal subject were separated into two subfractions, retained and nonretained, by immunoaffinity chromatography on monoclonal anti-apo B-100 Sepharose. Based on results of electrophoresis and radioimmunoassay, we have concluded that these two fractions represent apo B-48 and apo B-100 lipoproteins that we have named apo B-48 and apo B-100 VLDL. When compared to their respective apo B-100 VLDL, the apo B-48 VLDL from either Type III or Type IV was principally enriched in total lipids, in apo E, and had an electrophoretic migration similar to chylomicrons. This suggests that apo B-48 VLDL has the same origin (i.e., intestinal) in the two disorders. Both apo B-48 and apo B-100 VLDL were enriched in cholesteryl ester (CE) and depleted in triglyceride (TG) in Type III; however, both fractions were rich in TG and poor in CE in Type IV and in normal subjects. In addition, compared to their respective apo B-100 VLDL, the apo B-48 fraction was enriched in CE in Type III and in TG in Type IV. We conclude that, despite a possible similar origin for apo B-48 VLDL in Type III and in Type IV subjects, the composition of apo B-48 VLDL is variable and the CE/TG ratio is more characteristic of the type of hyperlipidemia than of the particular VLDL subfractions.
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PMID:Apolipoprotein B-48 and B-100 very low density lipoproteins. Comparison in dysbetalipoproteinemia (type III) and familial hypertriglyceridemia (type IV). 397 78

In view of the high incidence of hyperlipidemia and the low sialic acid content in the membranes of diabetics, we analyzed the percentage composition of apolipoprotein CII, known as an activator of lipoprotein lipase, and a subspecies of apolipoprotein CIII, an inhibitor of lipoprotein lipase, in triglyceride-rich lipoproteins. CIII can be sub-divided into three groups, CIII0, CIII1 and CIII2, according to sialic acid content by isoelectric focusing gel. In 82 diabetics, serum lipids and lipids in various lipoprotein fractions differed according to treatment, (diet, oral hypoglycemic drug or insulin). CIIIo/CII showed a positive correlation to plasma triglyceride and cholesterol. In the group receiving oral medication (N = 20), CIIIo/CII vs HDL-cholesterol showed a positive correlation, whereas CIII2/CII vs plasma triglyceride showed an inverse correlation. In the insulin group (N = 25), the percentage of CIIIo in VLDL apo C subspecies was inversely correlated with plasma cholesterol. In 38 diabetics whose HbA1 was also examined, CIIIo/CII increased with elevation of HbA1. CIIIo/CII in diabetics with HbA1 higher than 10% was significantly high compared with the index in other diabetics. The percentage of CIII1 in VLDL apo C subspecies was correlated to HbA1 level positively in the diet group but inversely in the insulin group. These results suggest that lipoprotein metabolism in diabetics may vary according to treatment and the sialylation of apolipoprotein may play an important role in determining the severity of this disease.
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PMID:Lipoprotein metabolism in diabetics treated with diet, oral hypoglycemic drug and insulin. 639 41

Two gene specific probes have been used to identify polymorphic DNA loci on chromosome 11 close to the insulin and apoprotein A-1 genes in a genetic analysis of hypertriglyceridaemic patients with and without co-existing diabetes. Of the 45 patients studied with both probes, 15 were diabetic of whom nine possessed class 3/3 insulin polymorphism genotypes, compared with none in the non-diabetic group (p less than 0.001; chi 2 test). In contrast, an uncommon apolipoprotein A-1 polymorphism was found to be equally distributed in the diabetic and the non-diabetic patients. No co-segregation of these two particular genetic polymorphisms was found in either patient group. The differing associations of the two disease-related polymorphism genotypes in patients with hypertriglyceridaemia with or without co-existing diabetes may possibly reflect differing aetiologies of the hyperlipidaemia.
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PMID:Insulin and apolipoprotein A-1/C-III gene polymorphisms relating to hypertriglyceridaemia and diabetes mellitus. 643 27

Amounts of plasma lipids, apolipoprotein AI (apo AI) and apolipoprotein E (apo E) were measured in streptozotocin-induced diabetic rats. Plasma triglyceride and cholesterol levels of diabetic rats were not significantly different from those of control rats. Plasma apo AI levels of diabetic rats were significantly higher than those of control rats (78.2 +/- 29.3 vs 27.2 +/- 3.4 mg/dl, P less than 0.001), while plasma apo E levels of diabetic rats were significantly lower than those of control rats (4.2 +/- 1.0 vs 13.9 +/- 5.3 mg/dl, P less than 0.001). Insulin treatment (12U/day) of diabetic rats decreased plasma apo AI levels significantly (treated: 32.8 +/- 3.4, untreated: 48.7 +/- 6.2, control: 28.5 +/- 2.4 mg/dl) and normalized plasma apo E levels (treated: 16.1 +/- 1.7, untreated: 5.4 +/- 0.7, control: 15.8 +/- 1.3). Insulin injection (4U/day) to normal rats did not cause any changes in both plasma apo AI and apo E levels. The data indicate that diabetes is not always accompanied by hyperlipidemia, however this inevitably carries apoprotein abnormalities characterized by the high plasma apo AI and low apo E levels, which are reversible with insulin treatment. The changes in the levels of plasma apo AI and apo E could be related to the development of atherosclerosis in diabetes.
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PMID:Reciprocal changes of plasma apo AI and apo E levels in streptozotocin-induced diabetic rats. 644 8

We analyzed the heterogeneity of apo E in very low density lipoprotein from 58 hyperlipidemic subjects with or without atherosclerosis, 69 patients with ischemic heart disease, and 100 apparently healthy individuals. Apo E gene frequencies in the group of healthy individuals were comparable with those in German and American populations. The distribution of six common apo E phenotypes in the groups of hyperlipidemia and ischemic heart disease was similar to that in the healthy group. In addition to the three major isoforms of apolipoprotein E (apo E-4, E-3, and E-2) and the new one (apo E-5) which was recently found in this laboratory, we have discovered an additional series of components, which showed themselves as at least three bands on an isoelectric focusing gel in the region of E-VII through E-V, in four patients with hyperlipidemia and atherosclerosis. The new series of apo E components, named apo E-Suita, was identical with the ordinary apo E in its interaction with heparin-Sepharose gel and with anti-apo E antibody. The most basic component of apo E-Suita (E-VII) was the unsialylated form and other components (E-VI and E-V), the sialylated forms. Family studies revealed that apo E-Suita was determined by inheritance of a new apo E allele located at the same locus as the hitherto known apo E components. Apo E-5 and apo E-Suita isoproteins had isoelectric points more basic than apo E-3, the parent type, by two and four units of charge, respectively. While the apo E-Suita isoprotein had the same molecular weight as ordinary major apo E isoproteins, the molecular weight of the apo E-5 isoprotein was approximately 1,500-2,000 lower than the other apo E isoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The incidence of abnormal apo E components, including apo E-5 and apo E-Suita, was high among patients with hyperlipidemia and ischemic heart disease (7:127), while we could not find such components among 100 healthy individuals. Moreover, five of seven patients with the abnormal apo E had overt atherosclerotic disease. The findings suggest that these kinds of apolipoprotein mutation are closely related to the development of atherosclerosis.
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PMID:New mutants of apolipoprotein E associated with atherosclerotic diseases but not to type III hyperlipoproteinemia. 648 Aug 26

The hyperlipidemias, with hypertension, diabetes mellitus and cigarette smoking, are amongst the major risk factors for the development of atheroma. The inter-relationships of hyperlipidemia and atheroma are complex but both appear to have a strong inherited component. Amongst the multiple genetic factors determining the common forms of hyperlipidemia, the apolipoprotein genes coding for the major peptides of the plasma lipoproteins (chylomicrons, VLDL, LDL and HDL) may be of particular relevance since the latter form a system of inter-converting particles for the delivery of lipid (triglyceride and cholesterol) to peripheral tissues (including the arterial wall). Recently several apolipoprotein genes have been isolated. Particularly interesting results have been obtained with the apolipoprotein AI and CIII genes. The DNA sequence of both genes and their immediate flanking region was determined. The two genes are physically linked and convergently transcribed. The cloning of the apolipoprotein genes made possible a detailed genetic study of patients with defects in lipid metabolism. An altered apo AI gene was shown to be inherited as a Mendelian trait linked to premature atherosclerosis in an affected family. Furthermore, the alteration of the apo AI gene seems to affect the expression of the apo CIII gene. Another DNA polymorphism that generates a new SstI site was shown to be present at low frequency (8%) in a random sample of the population. However, its frequency increased dramatically (42%) in a group of hypertriglyceridemic patients. It is thus not inconceivable that further studies of the genes involved in lipid metabolism will eventually help to replace the present phenotype based classification of lipid metabolism disorders by a genotype based system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein genes and hyperlipidemia. 649 70

In order to study the effects of chronic alcoholism, 3 groups of patients were investigated and compared to 10 healthy controls. Group I consisted of 9 heavy drinkers, who exhibited type V hyperlipidemia (HLP) under alcohol intake. Group II consisted of 7 patients, who previously had type V HLP under the influence of alcohol. At the time of the investigation, however, they had ceased alcohol drinking for at least 6 months and were normolipidemic. Group III consisted of 7 heavy drinkers without hyperlipidemia. Compared to controls, group I had significantly decreased plasma concentrations of high density lipoproteins2 (HDL2) and HDL3 (both P less than 0.01); activities of post-heparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) as well were excessively decreased (both P less than 0.01). In group III LPL was also decreased (P less than 0.01), but HTGL was distinctly (P less than 0.01) higher than in controls. No such differences could be demonstrated for the patients of group II. Acute alcohol withdrawal from a patient suffering from alcoholism with HLP led to a sharp increase of LPL with a simultaneous decrease of VLDL within 2 days and a more delayed increase of LDL, HDL2 and HTGL, all reaching normal values within 12 days after cessation of alcohol drinking. With respect to the apolipoprotein (apo) composition of HDL2, patients of group I and group III exhibited a significantly lower percentual content of apo C-I at the expense of a significantly higher content of apo A-II as compared to controls and patients of group II. In group I and II, the percentual content of apo D in HDL2 was significantly higher than in controls and in group III. It is concluded that severe alcohol intake strongly impairs LPL in patients with HLP. The pronounced increase of HTGL in some patients (group III) may protect these individuals from HLP. The increased content of apo D in HDL2 may be a possible primary trait for alcohol-inducible HLP.
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PMID:Post-heparin lipolytic activities and alterations of the chemical composition of high density lipoproteins in alcohol-induced type V hyperlipidemia. 649 35

Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients' S degrees f 0-20 lipoproteins possess a single peak with S degrees f rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S degrees f 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S degrees f 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL2b)gge at 11.0 nm and (HDL3b)gge at 7.8 nm. The major peak in the controls, (HDL3a)gge, was lacking in the patients. Gradient gel analysis of LDL indicated that patients' LDL possessed two peaks: a major one at 27 nm and a minor one at 26 nm. The electron microscopic structure of patients' lipoprotein fractions was indistinguishable from controls. Patients' HDL were spherical and contained a cholesteryl ester core, which suggests that lecithin/cholesterol acyltransferase was functional in the absence of apo AI. The effects of postprandial lipemia (100-g fat meal) were studied in patient 1. The major changes were the appearance of a 33-nm particle in the LDL density region of 1.036-1.041 g/ml and the presence of discoidal particles (12% of total particles) in the HDL region. The latter suggests that transformation of discs to spheres may be delayed in the patient. The simultaneous deficiency of apo AI and apo CIII suggests a dual defect in lipoprotein metabolism: one in triglyceride-rich lipoproteins and the other in HDL. The absence of apo CIII may result in accelerated catabolism of triglyceride-rich particles and an increased rate of LDL formation. Additionally, absence of apo CIII would favor rapid uptake of apo E-containing remnants by liver and peripheral cells. Excess cellular cholesterol would not be removed by the reverse cholesterol transport mechanism since HDL levels are exceedingly low and thus premature atherosclerosis occurs.
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PMID:Familial apolipoprotein AI and apolipoprotein CIII deficiency. Subclass distribution, composition, and morphology of lipoproteins in a disorder associated with premature atherosclerosis. 650 64

A patient with diabetes mellitus is described in whom an unusual xanthomatosis developed involving large areas of the subcutaneous tissue and vocal cords. Few lesions were present on the skin. Plasma lipid, lipoprotein, apolipoprotein, and cholestanol levels revealed normal patterns. Electron microscopy showed macrophages with vacuolar and crystal lipid inclusions. Results of lipid and enzyme analysis of the subcutaneous xanthoma were similar to those of xanthomas derived from a patient with diabetes mellitus and type V hyperlipidemia. The mechanism of this xanthomatosis remains unknown.
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PMID:Normolipemic subcutaneous xanthomatosis. 665 May 39

Normal plasma lipid levels do not prevent the infiltration of skin and arterial walls by cholesterol. This does not mean that lipoproteins do not play a role in tissue infiltration which takes place in subjects with normal lipids. Abnormal lipids, an abnormal distribution of atherogenic and non-atherogenic lipids in the blood, a latent hyperlipidemia, the relative proportions of apolipoproteins in circulation or an abnormal composition of the lipoproteins may contribute to this phenomenon. Our studies in subjects with normal lipid levels with xanthelasmata support the hypothesis that the apolipoprotein-B has atherogenic properties. In addition, they suggest that certain isomers of the apolipoprotein-E may also be involved. Preliminary studies in our laboratory using a simple technique of identifying the 6 phenotypes of the apolipoprotein-E suggest that the isomer E2 may favour the appearance of hyperlipidemia when another genetic or environmental factor is present.
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PMID:[Xanthoma and atherosclerosis in the presence of normal plasma lipids]. 665 Oct 70


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