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)

The hyperlipoproteinemias are disturbances in the metabolism of lipoproteins. Elevated levels of total and low density lipoprotein-cholesterol, and low levels of high density lipoprotein-cholesterol are proven risk factors for atherosclerosis. The significance of hypertriglyceridemia as an independent risk factor for atherosclerosis is controversial, however, at high levels triglycerides are a major risk factor for pancreatitis. Lipoprotein abnormalities can be divided into dietary, primary (genetic), and secondary disorders. The major causes of moderate and severe hypercholesterolemia are familial hypercholesterolemia, familial combined hyperlipidemia, severe primary (polygenic) hypercholesterolemia, and familial dysbetalipoproteinemia. Causes of hypertriglyceridemia include familial hypertriglyceridemia, familial lipoprotein lipase deficiency, sporadic hypertriglyceridemia, and secondary causes.
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PMID:Hyperlipoproteinemias: Part I. Lipoprotein classification and abnormalities. 194 97

To study the possible importance of the low density lipoprotein (LDL) receptor in regulating the degree of postprandial lipemia, a cholesterol-rich fat emulsion was infused into the duodenum of subjects who were divided into four groups based on the expected variation in the expression of the LDL receptor: young men (n = 11), elderly men (n = 7), male patients on estrogen therapy (n = 5), and patients with familial hypercholesterolemia (n = 9). In familial hypercholesterolemia, fasting plasma levels of lipoproteins of d less than 1.006 g/ml, intermediate density lipoproteins, and LDLs were increased. During the fat infusion, the cholesterol and triglyceride contents in the d less than 1.006 g/ml fraction increased to a similar extent in all groups, whereas a concomitant reduction of LDL cholesterol levels was observed. The degree of the decrease in LDL cholesterol was positively correlated with the observed increase in triglycerides in the d less than 1.006 g/ml fraction. There were no signs of accumulation of intermediate density lipoproteins during infusion in any of the groups studied. The results indicate that the capacity for clearance of chylomicrons and chylomicron remnants is not affected by variation in LDL receptor expression.
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PMID:Metabolism of lipoprotein remnants in humans. Studies during intestinal infusion of fat and cholesterol in subjects with varying expression of the low density lipoprotein receptor. 206 36

A subanalysis was performed on data acquired from 67 subjects having serum cholesterol levels of 6.2 mmol/l or above (greater than or equal to 240 mg/dl) and triglyceride levels of 2.25 to 4.00 mmol/l (199-354 mg/dl) (excluding patients with familial hypercholesterolemia), who were participating in a multicenter study comparing lovastatin and gemfibrozil, to evaluate the role of these agents in the treatment of combined hyperlipidemia (type IIb phenotype). In stratum 1 (cholesterol measures of 62.-7.79 mmol/l [240-301 mg/dl]), patients received either lovastatin 20 mg nightly (n = 17) or gemfibrozil 600 mg twice daily (n = 8), and in stratum 2 (cholesterol levels greater than or equal to 7.8 mmol/l [greater than or equal to 302 mg/dl]), patients received either lovastatin 40 mg nightly (n = 23) or gemfibrozil 600 mg b.i.d. (n = 19) for 6 weeks. Low-density lipoprotein (LDL) cholesterol levels were reduced significantly more by lovastatin than by gemfibrozil (stratum 1, -23 versus +1%, stratum 2, -34 versus -12%, respectively). A treatment goal of 4.0 mmol/l (155 mg/dl) for LDL cholesterol was achieved by 59 and 35% of patients receiving lovastatin and by 0 and 11% of patients receiving gemfibrozil in strata 1 and 2, respectively. Gemfibrozil was more effective in reducing triglyceride levels and in increasing high-density lipoprotein (HDL) cholesterol in both strata, although increases in HDL/LDL cholesterol ratios were greater with lovastatin. We conclude that, although lovastatin was more useful in normalizing LDL cholesterol, neither agent was ideal for all patients with combined hyperlipidemia. Further development of treatment regimens is called for in this group of patients.
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PMID:Treatment of combined hyperlipidemia with lovastatin versus gemfibrozil: a comparison study. 207 71

Hyperlipidaemia is a feature of glycogen storage disease type I (GSD-I) (Levy et al.). High levels of LDL cholesterol (200 +/- 25 mg dl-1) and apo B (387 +/- 44 mg dl-1) were found in association with hypercholesterolaemia in GSD-I. Related causative factors might be attributed to overproduction and/or delayed removal of LDL. In this study, a possible alteration in the clearance of LDL was examined. Using cultured fibroblasts for LDL receptor activity, the following observations were made: 1. GSD-I fibroblasts revealed only a slight decrease in LDL binding (65 +/- 7) when compared with controls (74 +/- 4 ng mg-1 protein), however, LDL internalization (382 +/- 24 vs. 570 +/- 52 ng mg-1 protein) and proteolytic degradation (2082 +/- 280 vs. 2916 +/- 12.5 ng mg-1 protein) were significantly affected (P less than 0.01). 2. Binding, internalization and proteolytic degradation of LDL from GSD-I were compared with that of controls, and were found to be significantly lower (P less than 0.01). 3. Substitution of control lipoprotein-deficient serum (LPDS) by GSD-I LPDS further diminished the above processes (P less than 0.05). Our results demonstrate that increased plasma cholesterol in GSD-I is due to a decreased catabolism of LDL. The data suggest that the problem may well be multifactorial, due to diminished receptor expression, abnormal LDL composition and impaired LDL receptor interaction due to a circulating inhibitory factor.
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PMID:Mechanisms of hypercholesterolaemia in glycogen storage disease type I: defective metabolism of low density lipoprotein in cultured skin fibroblasts. 211 85

Ninety-one children were determined to have hypercholesterolemia from a screening of 1,469 school children in the community near University of Tsukuba, and family studies of these children were performed. More than 50% of the parents participated in the study. The mean cholesterol levels of parents of hypercholesterolemic children were significantly higher than that of controls. Hypercholesterolemia in parents of hypercholesterolemic children was more frequent than that in controls. Nine families with autosomal dominant hyperlipidemia including familial hypercholesterolemia and familial combined hyperlipidemia were detected by further family studies. These results indicate that genetic factors are important as causes of hypercholesterolemia of school children and that family studies of hypercholesterolemic children is an efficient method for screening for persons with increased risk for cardiovascular diseases.
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PMID:[Family study of primary hypercholesterolemia in school children--the Tsukuba Study]. 213 86

Familial hypercholesterolemia is an inherited disease in humans that is associated with coronary artery disease and is caused by a deficiency of the receptor that mediates the internalization of low density lipoprotein (LDL). We have used an animal model for familial hypercholesterolemia, the Watanabe heritable hyperlipidemic (WHHL) rabbit, to design a therapeutic approach for this disease, which attempts to correct the hepatic defect in LDL receptor expression. Hepatocytes were harvested from WHHL rabbits, plated in primary cultures, and exposed to recombinant retroviruses capable of efficiently transferring a functional human LDL receptor gene. Genetically modified cells were harvested and infused into the portal vein of WHHL recipients, who were analyzed for metabolic consequences of human LDL receptor expression. Each animal exhibited a statistically significant decrease in total serum cholesterol 2-6 days after transplantation, with an eventual return to pretreatment levels. Proviral DNA sequences and virus-directed transcripts were detected in liver tissue 24 hr after transplantation. In situ hybridization demonstrated provirus expression in a small population of hepatocytes distributed in periportal sections of the liver. This study illustrates the potential of somatic gene therapy in ameliorating hyperlipidemia associated with familial hypercholesterolemia.
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PMID:Temporary amelioration of hyperlipidemia in low density lipoprotein receptor-deficient rabbits transplanted with genetically modified hepatocytes. 223 51

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

Because the reduced plasma oncotic pressure from hypoproteinemia causes hyperlipidemia, serum albumin levels should be maintained during low-density lipoprotein (LDL) apheresis. The amount of albumin loss was evaluated in seven patients with familial hypercholesterolemia during LDL apheresis in which columns packed with dextran sulfate-cellulose beads were used as a selective adsorbent of LDL. Serum albumin level significantly decreased from 4.3 +/- 0.3 (mean +/- SD) g/dl to 3.6 +/- 0.2 g/dl. The albumin loss was assessed by two different methods: 1) radioimmunoassay of microalbumin content in the discarded fluid, and 2) measurement of changes in plasma albumin reserve. The albumin losses during one apheresis session were 3.7 +/- 2.9 g and 8.3 +/- 5.7 g, respectively, depending upon which of two different methods was used. There was a significant correlation between these two methods (r = 0.84, p less than 0.02). The amount of albumin loss during apheresis was estimated to be between 4.1% and 9.1% of total plasma albumin reserve, and more than half of the decreased serum albumin level appeared to be attributable to dilution due to the electrolyte solution used for priming of the extracorporeal circuit.
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PMID:Evaluation of albumin loss during low-density lipoprotein apheresis. 226 88

The frequency of familial dyslipidemia syndromes was determined from blood tests in 33 objectively ascertained families with early coronary heart disease (CHD) (two or more siblings with CHD by the age of 55 years). Three fourths of persons with early CHD in these families had 90th percentile lipid abnormalities (cholesterol level at or above the 90th percentile, triglyceride level at or above the 90th percentile, and/or high-density lipoprotein cholesterol (HDL-C) level at or less than the 10th percentile). The HDL-C and triglyceride abnormalities were twice as common as low-density lipoprotein-cholesterol abnormalities. The most common syndromes found were familial combined hyperlipidemia (36% to 48% of families with CHD), familial dyslipidemic hypertension (21% to 54% of families with CHD), and isolated low levels of HDL-C (15%), with overlapping familial dyslipidemic hypertension with familial combined hyperlipidemia and low-level HDL-C. Well-defined monogenic syndromes were uncommon: familial hypercholesterolemia being 3% and familial type III hyperlipidemia, 3%. Another 15% of families with CHD had no lipid abnormalities at the 90th percentile. Physicians should learn to recognize and treat these common familial syndromes before the onset of CHD by evaluating family history and all three standard blood lipid determinations. Failure to recognize and treat them leaves affected family members at high risk of premature CHD.
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PMID:Population-based frequency of dyslipidemia syndromes in coronary-prone families in Utah. 231 Feb 76

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


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