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 hyperlipidemia associated with aging was characterized in the rat by comparing the plasma lipid, lipoprotein, and apolipoprotein profiles of adult (12 weeks old) and old (96 weeks old) male rats. Compared with those of the adult rats, the VLDL concentrations of the old rats were reduced, but IDL, LDL, and HDL concentrations were elevated. Despite a reduced VLDL concentration, concentrations of triglycerides in the plasma of the old rats were elevated. This phenomenon was attributed to an enrichment of triglyceride in the other lipoprotein fractions. In the old rats, hypercholesterolemia was the result of elevated IDL- and HDL-cholesterol whereas elevated plasma concentrations of apolipoproteins B and E were attributed to elevated LDL and HDL concentrations, respectively. Although concentrations of apolipoproteins A-I and A-IV did not change significantly in the plasma of the old rats, the distribution pattern of the apoA-IV was altered dramatically. Compared with the adult rats, a shift of apoA-IV in the HDL to the "lipoprotein-free" fraction was observed in the old rats, as measured by agarose gel chromatography. The data demonstrate that the hyperlipidemia in the old rats is associated with selective changes in the apolipoprotein profile.
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PMID:Changes in the concentrations and distributions of apolipoproteins of the aging rat. 717 76

Previous studies have shown that the A-IV-347Ser polymorphism is associated with the variability in low density lipoprotein (LDL)-cholesterol response to dietary therapy. The present study was designed to evaluate the association of this polymorphism with the individual variability observed in postprandial lipemic response. This polymorphism was characterized in 50 healthy male subjects homozygous for the apolipoprotein (apo)E3 allele. All subjects were subjected to a vitamin A-fat load test. Blood was drawn at time 0 and every hour over a period of 11 hours. Cholesterol and triglycerides (TG) in plasma and lipoprotein fractions of CH, TG, and retinyl palmitate (RP) were determined. Data from the postprandial lipemia revealed that subjects with the A-IV-347Ser allele (n = 14) have a lower postprandial response in total TG (P < 0.025), large triglyceride rich lipoproteins (TRL) TG (P < 0.02), and small-TRL TG levels (P < 0.007), and a higher postprandial response in large-TRL apoA-IV (P < 0.006) and apoB-100 (P < 0.041) levels than subjects homozygous for the A-IV-347Thr subjects (n = 36). In conclusion, the modifications observed in postprandial lipoprotein metabolism associated with this polymorphism within the apoA-IV gene locus may be involved in the variability in LDL-CH response observed in subjects consuming high saturated fat diets.
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PMID:Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus. 983 39

The aims of the study were to investigate associations of the apolipoprotein (apo) A-IV polymorphisms Thr347Ser and Gln360His with anthropomorphic measurements and fasting and postprandial lipids in subjects participating in the European Atherosclerosis Research Study II (EARS II). The allelic frequencies of Ser347 and His360 were 0.185 and 0.067, respectively, in the sample as a whole. There were no significant differences in rare allele frequency between cases (offspring of fathers who suffered a myocardial infarction before the age of 55 years) and controls. Control subjects who were carriers of Ser347 had significantly higher body mass indices (BMIs), waist:hip ratios, total and low density lipoprotein cholesterol and triacylglycerol (TG) concentrations (all P < or = 0.02) than control subjects who were non-carriers, but these effects were not seen in the cases. Control subjects who were carriers of His360 had lower BMIs (P = 0.04), cholesterol and TG concentrations (both P < or = 0.07) compared to non-carriers, but these effects were not seen in the cases. After consumption of an oral fat load, carriers of His360 who were most obese (subjects in the third tertile of BMI) had significantly reduced postprandial lipemia (P < 0.03, as assessed by area under the curve).-Fisher, R. M., H. Burke, V. Nicaud, C. Ehnholm, and S. E. Humphries. Effect of variation in the apoA-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II.
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PMID:Effect of variation in the apo A-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II. EARS Group. 992 58

The apolipoprotein (apo)A-I/C-III/A-IV gene cluster is involved in lipid metabolism and atherosclerosis. Overexpression of apoC-III in mice causes hypertriglyceridemia and induces atherogenesis, whereas overexpression of apoA-I or apoA-IV increases cholesterol in plasma high density lipoprotein (HDL) and protects against atherosclerosis. Each gene has been studied alone in transgenic mice but not in combination as the entire cluster. To determine which phenotype is produced by the expression of the entire gene cluster, transgenic mice were generated with a 33-kb human DNA fragment. The results showed that the transgene contained the necessary elements to direct hepatic and intestinal expression of the 3 genes. In the pooled data, plasma concentrations were 257+/-9, 7.1+/-0.5, and 1.0+/-0.2 mg/dL for human apoA-I, apoC-III, and apoA-IV, respectively (mean+/-SEM). Concentrations of these apolipoproteins were higher in males than in females. Human apoA-I and apoC-III concentrations were positively correlated, suggesting that they are coregulated. Transgenic mice exhibited gross hypertriglyceridemia and accumulation of apoB(48)-containing triglyceride-rich lipoproteins. Plasma triglyceride and cholesterol concentrations were correlated positively with human apoC-III concentration, and HDL cholesterol was correlated with apoA-I concentration. In an apoE-deficient background, despite being markedly hypertriglyceridemic, cluster transgenic animals compared with nontransgenic animals showed a 61% reduction in atherosclerosis. This suggests that apoA-I and/or apoA-IV can protect against atherosclerosis even in the presence of severe hyperlipidemia. These mice provide a new model for studies of the regulation of the 3 human genes in combination.
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PMID:Expression of human apolipoprotein A-I/C-III/A-IV gene cluster in mice induces hyperlipidemia but reduces atherogenesis. 1103 Dec 14

Apolipoprotein (apo) A-IV is a protein component of triglyceride-rich lipoproteins and high-density lipoproteins (HDL). In this study, two common genetic polymorphisms of the apoA-IV gene [codons 347(allele A and T) and 360 (allele 1 and 2)] were investigated in Greek patients with hyperlipidaemia and in healthy individuals matched for age, sex and smoking habits. In both study populations we evaluated the effect of these polymorphic sites on lipid and lipoprotein plasma levels and the body mass index (BMI). The frequencies of the 1/1 and 1/2 genotypes in codon 360 were 0.94 and 0.06 in hyperlipidemic patients and 0.92 and 0.08 in the control population, respectively. The frequencies of the A/A, A/T and T/T genotypes in codon 347 were 0.62, 0.34 and 0.04 in hyperlipidemic patients and 0.59, 0.33 and 0.08 in the control population, respectively. None of the above genotype frequency differences between the study populations reached statistical significance. The control population was not affected by any polymorphism of the apo A-IV gene. Hyperlipidaemic patients, carriers of the allele 2 (1/2 genotype), had significantly lower plasma triglyceride levels than carriers of the allele 1 (p = 0.03). Genetic variation in codon 347 had no influence on lipid and lipoprotein plasma levels. None of the polymorphisms at codons 360 and 347 affected the BMI. In conclusion, this study describes for the first time the genotype frequencies for polymorphic sites in codons 360 and 347 of the apo A-IV gene in a Greek population and suggests that the presence of the allele 2 is associated with lower plasma triglyceride levels in hyperlipidaemic patients.
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PMID:Genetic polymorphisms of the apolipoprotein A-IV in a Greek population and their relation to plasma lipid and lipoprotein levels. 1222 Apr 35