Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Report on a case of Tangier disease in a girl aged 4.11 m. Clinically the tonsils were hypertrophic and of a yellow color. Their stroma contained many cholesterinesters which produced the histologic picture of foam-cell xanthomatosis. The serum contained only traces of alpha-lipoprotein. The level of Cholesterin of the HDL fraction was reduced to one twelvth of the norm. The serum of her father also showed a clearly reduced content of HDL cholesterin. In the patient herself lipolytic enzymes like lecithin-cholesterin-acyltransferase, post-heparin plasma-lipoprotein lipase and hepatic triglycerid-lipase showed normal activity.
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PMID:["Hypo-alpha-lipoproteinemia" (Tangier-disease) (author's transl)]. 17 1

A review of radioimmunoassays for measuring human apolipoprotein B (apo B), the A apolipoproteins of high density lipoprotein (apo A-I and apo A-II) and apolipoprotein C-II (apo C-II) in human plasma and in isolated lipoproteins is presented. The sensitivity, specificity and validity of each of these assays is discussed. In normolipidemic subjects the reported serum apo B concentrations ranged between 0.83 +/- 0.16 and 0.92 +/- 0.21 g per l (m +/- SD). Serum apo B concentrations were highest in Type II subjects (Type IIa homozygotes 3.83 +/- 0.43 g per l; Type IIa heterozygotes 2.37 +/- 0.47 g per l) and were less elevated in patients with Type IV and Type V disorders (1.32 +/- 0.21 g per l and 1.26 +/- 0.30 g per l, respectively). Preliminary data on the relationship between plasma apo B and cholesterol, the distribution of apo B amongst the lipoprotein classes and a comparison of the lipoprotein lipid-apo B ratios in the various hyperlipidemic disorders are summarized. In contrast to apo A-II, the immunoreactivity of apo A-I was not fully exposed in whole sera and in isolated lipoproteins. The different methods used to measure the apo A-I immunoreactivity are discussed. In normolipidemic subjects the serum apo A-I concentration in males and females was 1.13 +/- 0.061 and 1.24 +/- 0.068 g per l (m +/- SD), respectively, while the corresponding serum apo A-II values were 0.35 +/- 0.038 g per l and 0.41 +/- 0.046 g per l. In subjects with Tangier's disease, the serum apo A-I and apo A-II concentrations were less than 1 percent and 5 to 7 percent of that found in controls. The serum apo A-I level was also reduced in two subjects with abetalipoproteinemia (0.38 g per l and 0.30 g per l) and Tye II hyperlipoproteinemia (range 0.54 to 0.86 g per l). In normotriglyceridemic subjects and those with Type IIa hyperlipoproteinemia, the total plasma apo C-II concentrations were 0.0497 +/- 0.0040 g per l and 0.0562 +/- 0.0054 g per l (m +/- SE). Plasma apo C-II levels in Type IIb, Type IV and Type V lipoproteinemic subjects were 0.0899 +/- 0.0046, 0.0854 +/- 0.0069 and 0.1328 +/- 0.0021 g per l, respectively and were significantly higher than in the normotriglyceridemic subjects. An analysis of the relationship between the apo C-II content and the lipoprotein lipase activator properties of VLDL isolated from normo- and hypertriglyceridemic plasma samples is presented.
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PMID:Recent progress in the development of radioimmunoassays for human serum lipoproteins. 20 63

Previous studies have shown that very low density lipoproteins (VLDL) from patients with Tangier disease are less effective as a substrate for human milk lipoprotein lipase (LPL) than VLDL from normal controls as assessed by measuring the first order rate constant (k1) of triglyceride hydrolysis. Tangier VLDL also has a higher content of apolipoprotein (apo) A-II than normal VLDL. To explore the possible relationship between the relatively high concentration of apoA-II in VLDL and low k1 values, Tangier VLDL were fractionated on an anti-apoA-II immunosorber. The retained fraction contained a newly identified triglyceride-rich lipoprotein characterized by the presence of apolipoproteins A-II, B, C-I, C-II, C-III, D, and E (LP-A-II:B:C:D:E or LP-A-II:B complex), whereas the unretained fraction consisted of previously identified triglyceride-rich apoB-containing lipoproteins free of apoA-II. In VLDL from patients with Tangier disease or type V hyperlipoproteinemia, the LP-A-II:B complex accounted for 70-90% and 25-70% of the total apoB content, respectively. The LP-A-II:B complexes had similar lipid and apolipoprotein composition; they were poor substrates for LPL as indicated by their low k1 values (0.014-0.016 min-1). In contrast, the apoA-II-free lipoproteins present in unretained fractions were effective substrates for LPL with k1 values equal to or greater than 0.0313 min-1. These results indicate that triglyceride-rich lipoproteins consist of several apoB-containing lipoproteins, including the LP-A-II:B complex, and that lipoprotein particles of similar size and density but distinct apolipoprotein composition also possess distinct metabolic properties.
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PMID:Isolation and characterization of an apoA-II-containing lipoprotein (LP-A-II:B complex) from plasma very low density lipoproteins of patients with Tangier disease and type V hyperlipoproteinemia. 190 45

The relationship between erythrocyte membrane structural and functional alterations and plasma lipids was studied in three patients with chylomicronemia due to either lipoprotein lipase (LPL) deficiency, apo C-II deficiency (in an individual who also suffers from thalassemia minor) or coexistent diabetes mellitus (and decreased LPL activity) and in a patient with Tangier disease. All of the patients' erythrocytes had significantly elevated phosphatidyl-choline (PC): sphingomyelin (Sph) ratios (most marked in the patient with Tangier disease). Major differences were observed in the PC: Sph ratios of erythrocytes and plasma. The pattern of changes in erythrocyte membrane enzyme activities differed despite similarities in the lipid composition of the erythrocytes. The changes in osmotic fragility (OF) were inversely related to the membrane cholesterol:phospholipid ratio. An even stronger negative correlation was found between OF at the lowest NaCl concentrations and the activities of both Na+,K+- and Mg++-ATPases. The ratio of total: surface sulfhydryl titres also correlated significantly with OF.
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PMID:Erythrocyte membrane alterations and plasma lipids in patients with chylomicronemia and in Tangier disease. 301 88

Mechanisms responsible for hypertriglyceridemia in Tangier disease were elucidated by an analysis of the plasma post-heparin lipolytic activities and the structural and metabolic properties of very low (VLDL) and low (LDL) density lipoproteins. The levels of lipoprotein lipase activity in six Tangier patients were significantly lower (P less than 0.001) than in 40 control subjects (8.1 +/- 3.3 (+/- S.D.) vs. 14.1 +/- 3.7 units/ml). In contrast, the levels of hepatic triacylglycerol lipase were higher (P less than 0.01) than in normal controls (14.4 +/- 3.9 vs. 9.3 +/- 4.0 units/ml). Because kinetic parameters such as Km or Vmax cannot be obtained with naturally occurring triacylglycerol-rich lipoproteins, the pseudo-first-order rate constant (k1) of triacylglycerol hydrolysis was used to assess the effectiveness of triacylglycerol-rich lipoproteins as substrates for lipoprotein lipase. The k1 values for Tangier VLDL (k1 = 0.017 +/- 0.002 min-1) were significantly lower (P less than 0.001) than the k1 values (0.036 +/- 0.008 min-1) for control VLDL. Both the Tangier and control LDL2 are similar in their resistance to the action of lipoprotein lipase, as shown by their low k1 values (0.002 +/- 0.001 and 0.001 +/- 0.001 min-1, respectively). The major compositional difference between the lipoproteins of Tangier disease and normal subjects was a significant increase in the percent content of apolipoprotein A-II in all lipoprotein particles with d less than 1.063 g/ml, with the greatest increase occurring in VLDL and the lowest in LDL2. These results were interpreted as indicating that, in Tangier disease, there is a lower reactivity of VLDL with lipoprotein lipase which may in part be attributed to the abnormal apolipoprotein composition. This finding, in conjunction with the reduced levels of lipoprotein lipase activity, may explain the hypertriglyceridemia in Tangier disease.
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PMID:Studies on the mechanism of hypertriglyceridemia in Tangier disease. Determination of plasma lipolytic activities, k1 values and apolipoprotein composition of the major lipoprotein density classes. 310 93

Deficiencies of lipoproteins occur as genetic disorders or may be presenting features of underlying disease. Familial high density lipoprotein (HDL), or alpha-lipoprotein, deficiency so far described includes Tangier disease, Lecithin: cholesterol acyltransferase (LCAT) deficiency, A-I Variants syndrome and Fish-eye disease. In 1981 Vergani described a familial aggregation of low HDL-cholesterol (less than 33 mg/dl) and Apo A (about 50% of normal levels) in the presence of normal VLDL and LDL-cholesterol. LCAT and lipoprotein lipase activities, both extrahepatic and hepatic, were normal. By zonal ultracentrifugation HDL2 subclass was found to be reduced. HDL apoproteins, examined by isoelectric focusing in polyacrylamide gel, were qualitatively normal. No disorders to which low levels of HDL might be secondary (e.g., overweight, cigarette smoking, nephropathy, liver disease) are present in the affected members. The underlying biochemical defect is unknown but probably involves altered synthesis or catabolism of HDL. Familial hypo-alpha-lipoproteinemia is accompanied by a high prevalence of premature myocardial infarction and sudden death. The genetic analysis of the disorder is consistent with autosomal inheritance. The criteria for the definition of familial hypo-alpha-lipoproteinemia are, therefore, as follows: 1) low HDL-cholesterol level in the presence of normal VLDL and LDL-cholesterol levels; 2) absence of diseases or factors to which hypo-alpha-lipoproteinemia might be secondary; 3) presence of a similar lipoprotein pattern in a first degree relative.
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PMID:[Familial hypoalphalipoproteinemia. Vergani's disease]. 665 16

A decreased level of HDL cholesterol (HDL-C) is the most common lipoprotein abnormality seen in people with premature coronary artery disease (CAD). In many cases, HDL-C reduction in patients with CAD may be the result of increased apo B-containing lipoprotein production by the liver with secondary hypoalphalipoproteinemia. Primary hypoalphalipoproteinemia is seen in approximately 4% of people with CAD. We report findings in four subjects with severe familial HDL deficiency (HDL-C << 5th percentile for age and sex; 0.08 to 0.38 mmol/L) in three French-Canadian kindreds with autosomal codominant inheritance. By inclusion criteria, all four subjects had normal fasting triglycerides and none were diabetic. HDL particle size by gradient gel electrophoresis revealed small HDL particles (estimated Stokes' diameter, 8.14 to 8.30 nm). Apo AI analysis by polyacrylamide gel electrophoresis and use of isoelectrofocusing gels in affected subjects revealed normal molecular weight (28.3 kD) and normal isoelectrofocusing point but a relative increase in proapoliprotein AI, with near-normal levels of proapolipoprotein AI in plasma, suggesting normal secretion of apo AI. Quantitative Southern blot analysis of the apo AI-CIII-AIV gene cluster reveals no gene rearrangements or allele deletion. Haplotypes of the apo AI gene, determined by use of the restriction enzymes Pst I, Xmn I, and Sst I and of the apo AII gene by use of the enzyme Msp I, did not reveal segregation of the low HDL-C trait with either the apo AI or the AII gene. Sequence analysis of the promoter region of the apo AI gene reveals heterozygosity for guanine-to-adenine substitution at position 76 in two kindreds with no evidence of segregation with the low HDL trait. None of the patients had mutations of the lipoprotein lipase gene common in subjects of French-Canadian descent. Haplotype analysis of the lipoprotein lipase gene did not show segregation with the low HDL trait. Plasma lecithin: cholesterol acyltransferase (LCAT) activity was found to be within normal levels in affected subjects and in nonaffected first-degree relatives. None of the affected subjects had clinical manifestations of Tangier disease. Two of the four cases examined, both men, had severe CAD and had undergone revascularization procedures. The third is a younger brother of one of these probands and the fourth is a 30-year-old woman, and both were free of clinical CAD. However, in none of the families did the low HDL trait unequivocally cosegregate with CAD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Severe familial HDL deficiency in French-Canadian kindreds. Clinical, biochemical, and molecular characterization. 762 90

The search for plasma lipoproteins began at the turn of the century. It was not until 1949 that a meeting of the Faraday Society celebrated the separation of the alpha and beta lipoproteins. At that moment, ultracentrifugists in Berkeley were already busily converting "alpha" to high density lipoprotein and "beta" to low density lipoprotein; the modern era of lipoproteins had begun. Over the succeeding 10 years, a quarrel over whether the level of Sf 0-20 or cholesterol was the more powerful risk factor ended with an eclipse of the analytical ultracentrifuge and a surge of interest in the biological side of lipoproteins. The postheparin clearing factor became lipoprotein lipase, and free fatty acids were discovered. In 1960, abetalipoproteinemia and Tangier disease suggested that the apolipoproteins must be specific and spurred a hunt for their number and nature. The first amino acid sequences aroused speculation of "amphipathic helices." By 1970, conversion of hyperlipidemia to five types of hyperlipoproteinemia led to worldwide fascination with electrophoretic patterns, "floating beta," and "the Friedewald formula" as codes for genetic abnormalities leading to early coronary artery disease. A few years later, the appearance of "familial combined hyperlipidemia" confounded the phenotyping, and the discovery of the low density lipoprotein receptor heralded the coming of true genotypes. This is a Bethesda-based story of the "climb to base camp" preceding the joining of molecular biology with the research on lipoproteins, dyslipoproteinemia, and atherosclerosis.
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PMID:Phenotyping. On reaching base camp (1950-1975). 846 75

Mutations in ABCA1 have been shown to be the cause of Tangier disease (TD) and some forms of familial hypoalphalipoproteinemia (HA), two genetic disorders characterized by low plasma HDL levels. Here we report six subjects with low HDL, carrying seven ABCA1 mutations, six of which are previously unreported. Two mutations (R557X and H160FsX173) were predicted to generate short truncated proteins; two mutations (E284K and Y482C) were located in the first extracellular loop and two (R1901S and Q2196H) in the C-terminal cytoplasmic domain of ABCA1. Two subjects found to be compound heterozygotes for ABCA1 mutations did not have overt clinical manifestations of TD. Three subjects, all with premature coronary artery disease (pCAD), had a combination of genetic defects. Besides being heterozygotes for ABCA1 mutations, two of them were also carriers of the R3500Q substitution in apolipoprotein B and the third was a carrier of N291S substitution in lipoprotein lipase. By extending family studies we identified 17 heterozygotes for ABCA1 mutations. Plasma HDL-C and Apo A-I values in these subjects were 38.3 and 36.9% lower than in unaffected family members and similar to the values found in heterozygotes for Apo A-I gene mutations which prevent Apo A-I synthesis. This survey underlines the allelic heterogeneity of ABCA1 mutations and suggests that: (i) TD subjects, if asymptomatic, may be overlooked and (ii) there may be a selection bias in genotyping towards carriers of ABCA1 mutations who have pCAD possibly related to a combination of genetic and environmental cardiovascular risk factors.
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PMID:Familial HDL deficiency due to ABCA1 gene mutations with or without other genetic lipoprotein disorders. 1501 41