Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen polymorphisms in six lipid transport genes were studied in a German population for relationships with dyslipidemia and coronary artery disease (CAD), to investigate a possible genetic basis for the marked differences in mortality rates from coronary heart disease within Europe. In other populations these polymorphisms have all been associated with CAD or with phenotypes known to predispose to CAD. The apoAI PstI polymorphism (P<0.005) and the lipoprotein lipase Ser(447)-Ter mutation (P<0.005) were associated with plasma triglyceride concentrations. Additionally, the apoAI PstI polymorphism (P<0.05), the apoB XbaI polymorphism (P<0.05) and apoE phenotypes (P<0.05) were associated with plasma cholesterol concentrations. However, none of the allele frequencies of the polymorphisms studied were related to the presence, or absence, of coronary artery disease. Associations between five polymorphisms representing four lipid transport gene loci and dyslipidemia were demonstrated in this German population. It is possible that predisposition to dyslipidemia in Germany involves a particular selection of polymorphic loci, which are different from those identified in other European countries.
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PMID:Coronary artery disease and dyslipidemia within Europe: genetic variants in lipid transport gene loci in German subjects with premature coronary artery disease. 1204 83

Hyperlipidemia and insulin resistance frequently develop after renal transplantation, contributing to cardiovascular disease. Individual differences in response based upon genetic variations in proteins regulating lipidic and glucose tolerance metabolism could be expected. In the general population, the S2 allelic variant of the apoprotein (apo) C-III gene has been associated with hypertriglyceridemia and an insulin resistant state, whereas the E4 allele of the apo E has been associated with hypercholesterolemia and atherosclerosis. Its influence in renal transplant patients remains to be seen. In order to assess the impact of apo E and C-III major polymorphisms on atherosclerotic vascular disease, lipid profile and impaired glucose tolerance in renal transplant patients, we studied 110 consecutively examined patients undergoing kidney transplantation (age range 24-73 years). Atherosclerotic complications were detected in 25% of patients, with age, male sex and hypercholesterolemia being significant atherosclerotic risk factors. Among the male patients with E4 allele, the odds ratio for coronary disease and global atherosclerosis were 10.2 (95% CI) and 6.4 (95% CI), respectively. There were no significant differences in the frequency of any of the polymorphisms among patients with dyslipidemia and impaired glucose tolerance. As the number of patients in our sample was small, larger studies are needed to verify these issues. While in the studied population C-III polymorphism appears to have little association with the prevalence of atherosclerotic complications, E4 allele should be considered as a genetic marker of coronary artery disease and global atherosclerosis in renal transplant patients.
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PMID:Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation. 1211 56

This review covers lipids, apolipoproteins, and receptors involved in the dyslipidemia of the nephrotic syndrome in humans and in rat or mouse models of the syndrome. It emphasizes research published during the last decade, though earlier work is cited. The focus is on the biosynthesis and catabolism of the plasma lipoprotein density classes and the role of receptors and enzymes in regulating lipoprotein metabolism in nephrosis. Although the factors responsible for the initiation of the hepatic and peripheral cellular responses to proteinuria and hypoalbuminemia remain elusive, recent work highlights the increased risk of atherosclerosis and the progression of renal disease associated with nephrotic dyslipidemia. Understanding of the role of the kidney in the catabolism of apolipoproteins entering the glomerular filtrate has been enhanced by the discovery of the receptor-mediated uptake of apolipoprotein A-I, the main apoprotein of HDL. The following aspects of lipid and lipoprotein metabolism in relation to nephrosis are discussed, with attention paid to differences between experimental nephrosis and the human nephrotic syndrome:(1) Albumin metabolism (2) Lipoprotein metabolism (3) Receptors (4) LCAT and CETP (5) Hepatic and Lipoprotein Lipase (6) Lipid metabolism (7) Lipiduria (8) Hypotheses and Questions (9) Summary.
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PMID:Lipoprotein metabolism in the nephrotic syndrome. 1213 20

High apoCIII concentration in apoB lipoproteins is a prominent component of atherogenic dyslipidemia, and explains the risk of coronary heart disease (CHD) associated with high triglyceride (TG). We hypothesized that diabetic people have atherogenic dyslipidemia with apoCIII in excess of that accounted for by their high TG levels. We selected 30 diabetic and 30 nondiabetic persons, 15 of each with fasting TG<160 mg/dl and 15 with TG>/=200 mg/dl. Using immunoaffinity chromatography and ultracentrifugation, we prepared large and small VLDL, IDL and LDL with or without apoCIII or apoE. The groups with TG>/=200 mg/dl, regardless of diabetes status, had higher concentrations of large and small VLDL particles with apoCIII and higher apoCIII concentrations than the groups with fasting TG<160 mg/dl. The diabetes groups did not have higher concentrations of these lipoproteins than the nondiabetes groups within the same fasting TG criteria. In conclusion, high concentrations of apoCIII-containing VLDL are associated with hypertriglyceridemia, which may play a critical role in identifying the high risk of CHD in hypertriglyceridemic patients whether diabetic or nondiabetic. Diabetes status per se does not appear to be associated with high concentrations of apoCIII-containing TG-rich lipoprotein particles, if the plasma TG levels are similar.
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PMID:Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease. 1281 12

Effects of high (100 and 80 kg) and moderate (60 kg) intensity static leg exercise on blood serum lipoproteins and apolipoproteins (apo) A1 and B were studied in healthy subjects (n=11) and patients with coronary heart disease and class I angina (n=11). Static leg exercise with loads exceeding 60 kg were associated with atherogenic changes of blood lipid transport system: elevation of levels of triglycerides, apoprotein B and apo B/A ratio both in healthy subjects and patients, and of total and low density lipoprotein cholesterol in patients. These post exercise changes were more pronounced in the presence of fasting hyperlipidemia and their severity increased with increase in duration of exercise. Static leg exercise did not increase concentration of high density lipoprotein cholesterol. For prevention of post exercise atherogenic dyslipidemia it is expedient to supplement strength training programs with dynamic exercise of moderate intensity.
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PMID:[Physical exercise and atherosclerosis: proatherogenic effects of high and moderate intensity static exercise on blood lipid transport system]. 1289 Dec 70

Dyslipidemia is a cardiovascular risk factor which commonly develops during forty. In Europe, progestins are frequently prescribed for treatment of perimenopausal symptoms in women in this age group, as well as in combination with estrogen replacement therapy in non hysterectomised postmenopausal women. Their complete metabolic tolerance is an important, even if non exclusive, factor to take in consideration for cardiovascular protection. Our aim was to review available data on the effects of a 19-norprogesterone derivative, nomegestrol acetate, on lipid tolerability. In healthy or at risk premenopausal women, clinical studies found no significant changes in lipid parameters (total, HDL and LDL cholesterol, triglycerides, apoprotein B, Lp(a) and LpA-I) with nomegestrol acetate administered in antigonadotropic sequence, alone or combined with estrogen in inverse sequence, during 6 to 9 cycles; there was only a small statistically significant decrease in apoprotein A1, probably due to the induced hypoestrogeny. In clinical studies carried out in postmenopausal women, nomegestrol acetate combined with estrogen replacement therapy in a sequential or continuous combined regimen, did not alter the beneficial estrogen-induced lipid profile: reductions in total and LDL cholesterol, apoprotein B and Lp(a); HDL cholesterol was unchanged and an increase in triglycerides occurred only with oral estrogens. A decrease in apoprotein A1 was found after six months of a cyclic sequential hormone replacement therapy but was associated with a beneficial increase in LpA-I. Nomegestrol acetate has proven its neutral effects on lipid metabolism and does not alter the beneficial estrogen-induced lipid effects.
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PMID:[Effects of a 19-norprogesterone derivative, the fourth decade nomegestrol acetate, on lipids]. 1291 65

Apolipoprotein E2, which has an R158 for C substitution, has reduced affinity for the LDL receptor and is associated with type III hyperlipoproteinemia in humans. Consistent with these observations, we have found that following adenovirus-mediated gene transfer, full-length apoE2 aggravates the hypercholesterolemia and induces hypertriglyceridemia in E-deficient mice and induces combined hyperlipidemia in C57BL/6 mice. Unexpectedly, the truncated apoE2-202 form that has an R158 for C substitution when expressed at levels similar to those of the full-length apoE2 normalized the cholesterol levels of E-deficient mice without induction of hypertriglyceridemia. The apoE2 truncation increased the affinity of POPC-apoE particles for the LDL receptor, and the full-length apoE2 had a dominant effect in VLDL triglyceride secretion. Hyperlipidemia in normal C57BL/6 mice was prevented by coinfection with equal doses of each, the apoE2 and the apoE2-202-expressing adenoviruses, indicating that truncated apoE forms have a dominant effect in remnant clearance. Hypertriglyceridemia was completely corrected by coinfection of mice with an adenovirus-expressing wild-type lipoprotein lipase, whereas an inactive lipoprotein lipase had a smaller effect. The findings suggest that the apoE2-induced dyslipidemia is not merely the result of substitution of R158 for C but results from increased secretion of a triglyceride-enriched VLDL that cannot undergo lipolysis, inhibition of LpL activity, and impaired clearance of chylomicron remnants. Infection of E(-)(/)(-)xLDLr(-)(/)(-) double-deficient mice with apoE2-202 did not affect the plasma cholesterol levels, and also did not induce hypertriglyceridemia. In contrast, apoE2 exacerbated the hypercholesterolemia and induced hypertriglyceridemia, suggesting that the LDL receptor is the predominant receptor in remnant clearance.
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PMID:Molecular mechanisms of type III hyperlipoproteinemia: The contribution of the carboxy-terminal domain of ApoE can account for the dyslipidemia that is associated with the E2/E2 phenotype. 1292 33

The aims of this study were to determine whether mice induced to become obese also exhibited accelerated atherosclerosis, and to determine whether obesity itself or dyslipidemia associated with obesity enhanced atherosclerosis. Wild-type (C57BL/6) mice and mice deficient for the low density lipoprotein receptor (LDLR-/-) or apolipoprotein E (apoE-/-) were fed a low fat, rodent chow diet or a high fat, high sucrose (diabetogenic) diet to induce obesity. As compared with wild-type mice, diabetogenic diet-fed LDLR-/- mice became more obese and developed severe dyslipidemia. Consequently, atherosclerotic lesions were increased in the LDLR-/- mice 3.7-fold over chow fed values. ApoE-/- mice showed weight gain profiles similar to those observed for wild-type mice. However, no differences in plasma lipid levels, lipoprotein profiles or atherosclerotic lesion areas were observed between chow-fed and diabetogenic diet-fed apoE-/- mice. These data demonstrate that lipid storage and partitioning as mediated by the low density lipoproteins (LDL) receptor or apoE-/- have profound and opposing consequences for dyslipidemia and atherosclerosis susceptibility associated with obesity.
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PMID:Mice deficient in apolipoprotein E but not LDL receptors are resistant to accelerated atherosclerosis associated with obesity. 1464 5

Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.
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PMID:Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain. 1472 62

In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue exhibit a full metabolic syndrome with visceral obesity, dyslipidemia, insulin-resistant diabetes, and hypertension. In this model, while systemic plasma GC levels are unaltered, GC delivery to the liver via the portal vein is increased. 11beta-HSD1 is most highly expressed in liver where inhibition or deficiency of its activity improves glucose and lipid homeostasis. To determine the potential contribution of elevated intrahepatic GCs alone toward development of insulin-resistant syndromes we generated transgenic mice expressing increased 11beta-HSD1 activity selectively in the liver under transcriptional control of hepatic regulatory sequences derived from the human apoE gene (apoE-HSD1). Transgenic lines with 2- and 5-fold-elevated 11beta-HSD1 activity exhibited mild insulin resistance without altered fat depot mass. ApoE-HSD1 transgenic mice exhibited fatty liver and dyslipidemia with increased hepatic lipid synthesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired hepatic lipid clearance. Further, apoE-HSD1 transgenic mice have a marked, transgene-dose-associated hypertension paralleled by incrementally increased liver angiotensinogen expression. These data suggest that elevated hepatic expression of 11beta-HSD1 may relate to the pathogenesis of specific fatty liver, insulin-resistant, and hypertensive syndromes without obesity in humans as may occur in, for example, myotonic dystrophy, and possibly, the metabolically obese, normal-weight individual.
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PMID:Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. 1511 95


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