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 purpose of this study was to examine the change in apolipoprotein and lipoprotein levels in patients with normolipidemic untreated non-insulin-dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for age, sex, body weight, alcohol consumption and cigarette smoking served as the control group. We observed that the concentrations of plasma total cholesterol (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C) were identical in both NIDDM and control groups. The levels of low-density lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group, but the difference did not reach statistical significance in our study. High-density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the apolipoprotein B (apo B) level remained similar to that of the control subjects. The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our results suggest that NIDDM patients are at higher risk of coronary heart disease, even if they remain normolipidemic.
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PMID:Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus. 135 44

The study objective was to determine the effects of monotherapy with clonidine and atenolol versus placebo on serum lipids, apolipoproteins, and blood pressure in patients with mild primary hypertension. The protocol comprised a double blind, randomized, placebo-controlled 5-month prospective study carried out in an outpatient general internal medicine clinic in a university medical center. There were 92 patients ages 18 to 70, with mild primary hypertension (sitting diastolic blood pressure of greater than 90 mm Hg and less than 105 mm Hg) without significant cardiac, renal, cerebrovascular, hepatic, neoplastic, or hematologic disorders. Patients with severe hyperlipidemia or peripheral vascular disease were also excluded. All factors known to effect serum lipids were held constant throughout the study (i.e., diet, weight, exercise, caffeine, tobacco). Atenolol and clonidine significantly reduced blood pressure when compared with placebo. Atenolol caused significant increases in serum triglycerides and apolipoprotein B (p less than 0.05) and significant reductions in high-density lipoprotein-cholesterol, apolipoproteins A-I and A-II (p less than 0.05). Atenolol also induced a significant adverse effect on all lipid ratios, increasing total cholesterol/high density lipoprotein-cholesterol, low density lipoprotein-cholesterol/high density lipoprotein-cholesterol, apolipoprotein B/apolipoprotein A-I and apolipoprotein B/apolipoprotein A-II ratios and decreasing low density lipoprotein-cholesterol/apolipoprotein-B ratio (p less than 0.05). Clonidine caused significant reductions in high-density lipoprotein-cholesterol, apolipoproteins AI and AII (p less than 0.05 but was neutral on all other lipids, lipid subfractions, and apolipoproteins. Clonidine did not significantly alter any of the lipid ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension. 219 93

A quantitative automated immunoturbidimetric procedure for the analysis of apolipoprotein A-II (Apo A-II) in human serum is described. Dilution of antibody with a 5% solution of PEG 6000 enhanced the quantification. The within- and between-assay coefficients of variation were less than 5%. Results correlated well with those obtained by classic electroimmunodiffusion and immunonephelometry. No extraction of samples with organic solvent was necessary, whatever the triglyceride concentration. Large lipoproteins such as VLDL and immunocomplexes did not affect the method, nor was there interference from icteric or hemolyzed serum or from serum with excessive hyperlipemia. Physiological values of Apo A-II were determined in a normal population. Concentrations were found to be age-dependent, and higher in women than in men. The procedure is very suitable for the rapid, precise, reproducible and inexpensive assay of Apo A-II.
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PMID:Automated immunoturbidimetric assay of serum apolipoprotein A-II using the Cobas-Bio centrifugal analyser: influence of hyperlipoproteinemia. 393 44

The plasma concentration, particle size, and chemical composition of high density lipoproteins (HDLs) are associated with the metabolism of triglyceride-rich lipoproteins (TGRLs). During alimentary lipemia there is active exchange of lipids and apolipoproteins between HDL and apolipoprotein B-containing lipoproteins. Whereas HDL has been assigned a protective role against the development of atherosclerosis, alimentary lipemia has been proposed to represent a potentially atherogenic state. We examined plasma HDL concentration, particle size, and composition and their relations to postprandial TGRLs in 32 postinfarction patients and 10 healthy control subjects after intake of a standardized oral fat load of a mixed-meal type. All patients had undergone coronary angiographies in connection with the myocardial infarction and around 5 years thereafter. The plasma HDL cholesterol concentration decreased significantly in response to the oral fat load, particularly in hypertriglyceridemic patients, with a concomitant increase of HDL triglycerides. A limited and reversible yet consistent increase of HDL particle size (1-2%) was seen 6 hours after intake of the oral fat load on nondenaturing gradient gel electrophoresis (GGE) in both patients and control subjects. Virtually no changes in the plasma concentration of HDL GGE subclasses, lipoproteins containing apolipoprotein A-I but no apolipoprotein A-II (LpA-I), or lipoproteins containing both apolipoproteins A-I and A-II (LpA-I:A-II) were induced in the postprandial state despite massive increases of large very low density lipoprotein (VLDL) and large chylomicron remnant levels (determined as apolipoproteins B-100 and B-48 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Strong inverse correlations with fasting plasma HDL cholesterol and the larger HDL GGE subspecies were found for large postprandial VLDL and large chylomicron remnants, whereas the corresponding relations for small VLDL and small chylomicron remnants were weaker. The relations of both large and small VLDL and chylomicron remnants to HDL cholesterol were confined to subjects in the lower fasting plasma HDL cholesterol range (< 1.2 mmol/l). None of the HDL parameters measured, either in the fasting or in the postprandial state (HDL cholesterol, HDL triglycerides, HDL GGE subclasses, LpA-I, and LpA-I:A-II), were related to the development of coronary atherosclerosis, whereas the postprandial plasma levels of small chylomicron remnants, which showed weak negative correlations with HDL, related positively to the progression of coronary atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:HDLs and alimentary lipemia. Studies in men with previous myocardial infarction at a young age. 842 32

More than half of the patients with angiographically confirmed premature coronary heart disease (CHD) have a familial lipoprotein disorder. Familial combined hyperlipidaemia (FCHL) represents the most common genetic dyslipidemia with a prevalence of 1.0-2.0%. FCHL is estimated to cause 10-20% of premature CHD and is characterized by elevated levels of cholesterol, triglycerides, or both. Attempts to characterize genes predisposing to FCHL have been hampered by its equivocal phenotype definition, unknown mode of inheritance and genetic heterogeneity. In order to minimize genetic heterogeneity, we chose 31 extended FCHL families from the isolated Finnish population that fulfilled strictly defined criteria for the phenotype status. We performed linkage analyses with markers from ten chromosomal regions that contain lipid-metabolism candidate genes. One marker, D1S104, adjacent to the apolipoprotein A-II (APOA2) gene on chromosome 1, revealed a lod score of Z = 3.50 assuming a dominant mode of inheritance. Multipoint analysis combining information from D1S104 and the neighbouring marker D1S1677 resulted in a lod score of 5.93. Physical positioning of known genes in the area (APOA2 and three selectin genes) outside the linked region suggests a novel locus for FCHL on 1q21-q23. A second paper in this issue (Castellani et al.) reports the identification of a mouse combined hyperlipidaemia locus in the syntenic region of the mouse genome, thus further implicating a gene in this region in the aetiology of FCHL.
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PMID:Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23. 953 21

We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal compared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected by cigarette smoking, we investigated 12 male smokers and 12 non-smokers with comparable fasting lipoprotein profile, BMI, and age. Plasma samples obtained after an overnight fast and postprandially were separated by density gradient ultracentrifugation. Postprandial apoA-I, lipoprotein AI-particles (LpA-I), HDL-cholesterol, and HDL apoE concentrations decreased in smokers, but remained unchanged in controls. Concomitantly, cholesterol and apoE concentrations increased significantly in TRL fractions in smokers. Fasting lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) activity levels, as well as esterification rates (EST) and phospholipid transfer rates were comparable between the groups. Cholesteryl ester transfer protein (CETP) activity levels were lower in the smokers. Postprandially EST increased, but CETP and PLTP activities deceased in smokers as compared to controls. We conclude, that even healthy, normolipidemic smokers have altered postprandial high density lipoprotein (HDL) cholesterol and apolipoprotein composition, as well as lipid transfer protein activities. The shift of cholesterol and apoE from HDL to the triglyceride-rich lipoprotein (TRL) fraction, together with decreased plasma apoA-I and LpA-I concentrations during alimentary lipemia may indicate impaired reverse cholesterol transport. Both the postprandial increase in TRL and the lowering of HDL may promote atherogenesis in smokers.
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PMID:Decreased postprandial high density lipoprotein cholesterol and apolipoproteins A-I and E in normolipidemic smoking men: relations with lipid transfer proteins and LCAT activities. 968 53

To identify quantitative trait loci (QTLs) responsible for regulating plasma lipid concentration associated with obesity, linkage analysis was carried out on the 190 F2 progeny of a cross between C57BL/6J female and KK-Ay (Ay allele at the agouti locus congenic) male. In F2 a/a (agouti locus genotype) mice, two QTLs were identified on chromosome 1 and a QTL on chromosome 3 for total-cholesterol. A QTL for HDL-cholesterol was identified on chromosome 1 and a QTL for NEFA on chromosome 9. In F2 Ay/a mice, two QTLs for HDL-cholesterol were found on chromosome 1. Loci for other lipids with suggestive linkage were also identified. In both F2 mice, one QTL on chromosome 1 for total- and HDL-cholesterol was mapped near D1Mit150, in the vicinity of the apolipoprotein A-II (Apoa2) locus. Seven nucleotide substitutions out of 309 nucleotide apolipoprotein A-II cDNA sequences were identified between KK and C57BL/6J. The Ay allele may be an indication of the plasma lipid levels, but its influence was less apparent than in the case of weight control. The loci for lipids were not on identical chromosomes with those previously identified for obesity, suggesting that hyperlipidemia in KK does not coincidentally occur with obesity.
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PMID:Quantitative trait loci that regulate plasma lipid concentration in hereditary obese KK and KK-Ay mice. 1010 Dec 57

We examined familial combined hyperlipidemia (FCHL) families from nonisolated regions in Germany and China to see if we could corroborate support for a chromosome 1q FCHL locus in more general populations. We recruited 24 German families with 137 members, 92 of whom met the criteria of affected in terms of the low density lipoprotein (LDL) and triglyceride levels in excess of the 90th percentile for age and gender. In China, we recruited 12 families with a total of 81 members. All affected persons had total cholesterol concentrations >240 mg/dl and triglyceride concentrations >250 mg/dl. We examined the markers APOA2, D1S1677, D1S104, D1S194, D1S426, and D1S196. Two-point linkage analysis allowing for heterogeneity gave a maximum linkage of disorder score (HLOD) of 2.60 right over D1S194, estimating the proportion of linked families at 36%. This marker is adjacent to D1S104. The evidence for linkage was roughly the same both in the German (HLOD 1.40) and Chinese families (HLOD 1.52). Marker D1S194 is close to the retinoid X receptor (RXR) gene locus, which was found to be linked to triglyceride levels in an earlier twin study from our laboratory. We interpret our observations as encouraging support for the recent findings indicating the presence of a gene for FCHL on chromosome 1q. Furthermore, since DIS194 is adjacent to the gene for the RXR, we suggest that RXR is an attractive candidate for involvement in FCHL.
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PMID:Support for linkage of familial combined hyperlipidemia to chromosome 1q21-q23 in Chinese and German families. 1073 33

Familial combined hyperlipidemia (FCHL) is a common inherited hyperlipidemia and a major risk factor for atherothrombotic cardiovascular disease. The cause(s) leading to FCHL are largely unknown, but the existence of unidentified "major" genes that would increase VLDL production and of "modifier" genes that would influence the phenotype of the disease has been proposed. Expression of apolipoprotein A-II (apoA-II), a high density lipoprotein (HDL) of unknown function, in transgenic mice produced increased concentration of apoB-containing lipoproteins and decreased HDL. Here we show that expression of human apoA-II in apoE-deficient mice induces a dose-dependent increase in VLDL, resulting in plasma triglyceride elevations of up to 24-fold in a mouse line that has 2-fold the concentration of human apoA-II of normolipidemic humans, as well as other well-known characteristics of FCHL: increased concentrations of cholesterol, triglyceride, and apoB in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL), reduced HDL cholesterol, normal lipoprotein lipase and hepatic lipase activities, increased production of VLDL triglycerides, and increased susceptibility to atherosclerosis. However, FCHL patients do not have plasma concentrations of human apoA-II as high as those of apoE-deficient mice overexpressing human apoA-II, and the apoA-II gene has not been linked to FCHL in genome-wide scans. Therefore, the apoA-II gene could be a "modifier" FCHL gene influencing the phenotype of the disease in some individuals through unkown mechanisms including an action on a "major" FCHL gene. We conclude that apoE-deficient mice overexpressing human apoA-II constitute useful animal models with which to study the mechanisms leading to overproduction of VLDL, and that apoA-II may function to regulate VLDL production.
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PMID:Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia. 1094 21

The hypolipidemic fibric acid drugs are peroxisome proliferator-activated receptor a (PPAR alpha) ligands. PPAR alpha activated by fibric acids form heterodimers with the 9-cis retinoic acid receptor (RXR). The PPAR/RXR heterodimers bind to peroxisome proliferator response elements (PPRE), which are located in numerous gene promoters and increase the level of the expression of mRNAs encoded by PPAR alpha target genes. Fibric acids decrease triglyceride plasma levels through increases in the expression of genes involved in fatty acid-beta oxidation. Furthermore, they decrease triglycerides by increasing lipoprotein lipase gene expression and by decreasing apolipoprotein C-III gene expression. Fibric acids increase high-density lipoprotein (HDL) cholesterol partly by increasing apolipoprotein A-I and apolipoprotein A-II gene expression. Fibric acids also reduce vascular wall inflammation and the expression of genes involved in different vascular functions (ie, vasomotricity, thrombosis). Fibric acids are used to treat primary hypertriglyceridemia and mixed hyperlipidemia. Some fibric acid molecules are active in essential hypercholesterolemia. Clinical evidence shows that fibric acids reduce coronary atherosclerosis progression in dyslipidemic patients (eg, bezafibrate, gemfibrozil) and in type 2 diabetic patients (fenofibrate). Gemfibrozil decreases coronary morbidity and mortality in patients with low HDL cholesterol, normal triglycerides,and normal low-density lipoprotein (LDL) cholesterol plasma levels. Further clinical studies are necessary to investigate if fibric acids decrease cardiovascular mortality in type 2 diabetes and in primary prevention of hypertriglyceridemia and hypolipidemia.
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PMID:The role of fibric acids in atherosclerosis. 1112 53


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