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)

We have characterized the clinical and biochemical features of three siblings of a kindred with severe hypertriglyceridaemia due to apolipoprotein C-II (apo C-II) deficiency caused by the mutation described as apo C-IIHamburg. The clinical syndrome is characterized by recurrent pancreatitis in two of three affected individuals, with discrete hepatosplenomegaly in all three patients and cholelithiasis in one. Eruptive xanthomas and lipemia retinalis were absent. Plasma lipoproteins were characterized by fasting chylomicronaemia, reduced low density lipoproteins (LDL) and low high density lipoproteins (HDL). The marked hypertriglyceridaemia could be corrected promptly by infusion of normal plasma. Apolipoprotein C-II (apo C-II) levels in homozygotes were very low (0.01 mg dl-1), and mean apo C-II levels in heterozygotes were lower (2.08 +/- 0.11 mg dl-1) than in normal family members (3.38 +/- 0.75 mg dl-1). Lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma were normal. Zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins and reduced LDL and HDL. LDL consisted of two fractions with higher hydrated density of the main fraction compared with normals with a trend to normalization on a fat-free diet. The molecular defect in the apo C-II Hamburg gene has been previously identified as a donor splice site mutation in the second intron. This leads to abnormal splicing of the apo C-II Hamburg mRNA and apo C-II deficiency in plasma. The mutation causes the loss of an HphI restriction enzyme site present in the normal apo C-II gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein C-II deficiency syndrome due to apo C-IIHamburg: clinical and biochemical features and HphI restriction enzyme polymorphism. 134 86

We have isolated an isoform of the protein activator of lipoprotein lipase, apolipoprotein C-II, from the very low density lipoproteins of four patients of African ancestry with hypertriglyceridemia and eruptive or pedunculated xanthomata. This protein, which we designate apolipoprotein C-II2, differs from the previously recognized species, which we denote apolipoprotein C-II1, by substitution of glutamine for lysine at residue 55, a mutation which would require only a single-base substitution in the structural gene for apolipoprotein C-II1. Each of the patients in whom apolipoprotein C-II2 was found had approximately equal amounts of apolipoprotein C-II1 and apolipoprotein C-II2 among the apoproteins of the very low density lipoproteins, suggesting that the structural genes for these proteins are allelic. Two additional apparent heterozygotes were found among the first-degree relatives of each of two of the patients in patterns compatible with monogenic autosomal transmission. Approximately equal amounts of apolipoproteins C-II2 and C-II1 were also found by isoelectric focusing in 6 of a casual series of 50 normolipidemic blacks, but none or only trace amounts of apolipoprotein C-II2 were found in 500 samples from Caucasian subjects with hyperlipidemia. These findings suggest that this polymorphism is distributed primarily among blacks, possibly reflecting some positive Darwinian selection pressure. Whether this polymorphism has a modifying effect upon the development of hyperlipemia remains to be determined.
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PMID:A variant primary structure of apolipoprotein C-II in individuals of African descent. 394 71

A new rare mutant form of apolipoprotein C-II (apoC-II), designated apoC-IISF, was identified in three unrelated hyperlipidemic patients. The first was a Caucasian male with a total cholesterol (TC) of 313 mg/dl and total triglyceride (TG) of 282 mg/dl, the second an African-American female (TC 345 mg/dl, TG 203 mg/dl) and the third, an African-American male (TC 345 mg/dl, TG 1000 mg/dl). Each subject was found to be heterozygous for a G to A substitution in the codon for residue 38, resulting in a Lys for Glu exchange. This accounts for the increased pl value of 5.3. The third patient, in addition to apoC-IISF, had apoC-II2, another charge variant. This was determined by DNA sequencing, confirming the Gln for Lys change at residue 55 previously predicted by analysis of peptide fragments in this laboratory. Similar Michaelis constants of activation and activation energies were observed when the ability of apoC-IISF to activate lipoprotein lipase was compared to normal apoC-II. This indicates that major changes in charge around residue 38 lack effect on the activation properties. The variant may be altered in some other property, such as lipid binding, but since the distribution of apoC-IISF revealed no simple co-inheritance with lipid levels, it is unclear to what extent it plays a role in the observed hyperlipidemia. The presence of other factors acting together with the variant may predispose to elevated lipid levels.
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PMID:Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia. 849 Jun 26

Disorders in lipoprotein metabolism (dyslipidemia) can result in premature atherosclerosis or pancreatitis. Dyslipidemias can be classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low density lipoprotein cholesterol and decreased levels of HDL cholesterol predispose to premature atherosclerosis. Triglyceride levels greater than 1,000 mg/dL increase the risk for pancreatitis. In the appraisal of the dyslipidemias, measurement of serum cholesterol, triglycerides, HDL-cholesterol and obtaining the LDL cholesterol by Friedewald equation is usually sufficient in the majority of patients. However, in some cases, such as the diagnosis of the Type III dyslipidemia and when triglycerides are > or = 400 mg/dL, ultracentrifugation is required to determine the VLDL or LDL cholesterol. Lipoprotein electrophoresis can be useful in the diagnosis of Type III dyslipidemia (broad beta band) and also to detect chylomicrons. In young subjects with coronary artery disease with a normal LDL cholesterol an apolipoprotein B-100 level may be a useful test. In children and young adults with severe hypertriglyceridemia, measurement of lipoprotein lipase activity or assaying apolipoprotein C-II levels can be useful in elucidating the cause. Also, laboratory tests are useful in excluding a secondary cause of dyslipidemia (urinalysis, plasma creatinine, TSH, glucose, protein electrophoresis, alkaline phosphatase and transaminases). Thus, laboratory investigations play an important role in the management of dyslipidemia.
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PMID:A practical approach to the laboratory diagnosis of dyslipidemia. 870 23

The effect of acarbose, an alpha-glucosidase inhibitor, on postprandial glucose and lipid metabolism was investigated in patients with type 2 diabetes mellitus. Twenty patients (10 men and 10 women) with type 2 diabetes mellitus were studied. A test meal was taken with or without 100 mg of acarbose. The levels of plasma glucose, and serum immunoreactive insulin, lipids, apolipoproteins, and remnant-like particle cholesterol were investigated. Acarbose inhibited the postprandial increase of both plasma glucose and serum immunoreactive insulin. Acarbose also significantly suppressed the increase of serum triglycerides at 60, 90, and 120 min (P < 0.05 to P < 0.01), and the increase of serum remnant-like particle cholesterol at 60 and 120 min (P < 0.05). Acarbose inhibited the postprandial decline of apolipoprotein C-II, and decreased the postprandial serum apolipoprotein C-III level. These results suggest that acarbose may improve postprandial hyperlipidemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.
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PMID:Effect of acarbose on postprandial lipid metabolism in type 2 diabetes mellitus. 976 72

Primary Hyperchylomicronemia is known as a syndrome in which the accumulation of chylomicron occurs in the circulation. The main clinical symptoms of this disorder are the huge increase in plasma trigriceride and cholesterol, and the presence of xanthomatous eruption, lipemia retinalis, hepatosplenomegaly, and the complication of acute pancreatitis. With gene analysis, a deficiency of lipopreteinlipase (LPL) or apolipoprotein C-II is revealed as a main cause of primary chylomicronemia. Furthermore, in some cases, abnormalities of remnant receptors, the presence of antibody against LDL, apolipoprotein C-II, and LDL receptor are reported as causes of chylomicronemia syndrome. In the present paper, we summarized the major gene polymorphism and characteristics of clinical symptom of these disease.
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PMID:[Primary hyperchylomicronemia and gene defects]. 1063 9

The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and massive accumulation of chylomicrons in plasma. This hypertriglyceridemia can lead to the development of eruptive xanthomas, lipemia retinalis, and is clinically important when plasma triglyceride levels predispose to pancreatitis (above 2000 mg/dl). Three genetic disorders have been described in which chylomicrons accumulate in plasma: familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency, and familial inhibitor to lipoprotein lipase. In addition, chylomicronemia is seen in other states with the simultaneous occurrence of familial forms of moderate hypertriglyceridemia and other acquired causes for hypertriglyceridemia such as diabetes mellitus, certain drug therapies and alcohol use. Treatment should be directed at both the familial and the acquired disorder. This review discusses the chylomicronemia syndrome presenting the pathophysiologic characteristics of triglyceride and chylomicrons metabolism, diagnosis, prevalence and treatment.
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PMID:[Chylomicronemia syndrome]. 1190 95

Severe hypertriglyceridemia is a rare condition in pregnancy. All the cases of severe gestational hypertriglyceridemia that have been reported previously in the literature were caused by genetic mutations or familial hypertriglyceridemia secondary to lipoprotein lipase deficiency or apolipoprotein C-II deficiency. We report the first case of severe, non-genetic, non-familial, pregnancy-induced hypertriglyceridemia. The genetic underlying causes were excluded by molecular genetic investigation. The reported case was managed solely by strict dietary control. Hypertriglyceridemia was diagnosed incidentally during pregnancy, in this case, while taking a blood sample to check her hemoglobin level. Acute pancreatitis, which is a relatively common life threatening complication of this condition, was avoided. This report reviews the subtypes of hyperlipidemia, clinical picture, antenatal management and its effect on pregnancy and vice versa. It is important that the clinician has a clear understanding of the normal lipid profile during pregnancy, the clinical picture, the potential complications, available treatment options of hypertriglyceridemia particularly during pregnancy. The timing and route of delivery should be individualized.
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PMID:Severe, gestational, non-familial, non-genetic hypertriglyceridemia. 1744 93

Familial chylomicronemia syndrome is a rare disorder of lipoprotein metabolism due to familial lipoprotein lipase or apolipoprotein C-II deficiency or the presence of inhibitors to lipoprotein lipase. It manifests as eruptive xanthomas, acute pancreatitis, and lipaemic plasma due to marked elevation of triglyceride and chylomicrons levels. We report a rare case of familial chylomicronemia in a 9-month-old infant, who was diagnosed after his plasma was incidentally found to be milky. Lipid profile showed familial chylomicronemia (Type 1 Hyperlipidemia). The infant was started on a low fat diet and advised a regular follow-up.
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PMID:Familial chylomicronemia in a nine months old infant. 1894 Jan 29

Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. Characteristics for dyslipidemia in the metabolic syndrome are elevated fasting and postprandial triglyceride (TG) and decreased high-density lipoprotein-cholesterol (HDL-C). Diacylglycerol(DAG) has been suggested to suppress postprandial hyperlipidemia and promote negative caloric balance by increasing energy expenditure, due to intestinal physiochemical dynamics that differ from triacylglycerol (TAG). Our study (Study 1) demonstrated that DAG suppressed postprandial increase in TG-rich lipoprotein, very low density lipoprotein (VLDL), and insulin as compared with TAG in young male individuals. Further, our another study using the apolipoprotein C-II deficient subject demonstrated that DAG suppressed postprandial increase in VLDL-cholesterol and remnant-like particle-cholesterol compared with TAG, suggesting that DAG suppress postprandial TG-rich lipoprotein independent of lipoprotein lipase. Study 1 also showed that DAG significantly increased plasma serotonin, which is mostly present in intestine and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our studies presented DAG-mediated amelioration in postprandial TG-rich lipoprotein, insulin, and energy metabolism, indicating the therapeutic application of DAG for the metabolic syndrome.
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PMID:[Therapeutic application of diacylglycerol oil for the metabolic syndrome]. 2016 43


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