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)

Apolipoproteins AIV, B, E, and the Lp(a) glycoprotein are genetically polymorphic in humans. Three common alleles epsilon 2, epsilon 3 and epsilon 4 control the polymorphism of apolipoprotein E. These code for proteins which differ in functional properties, e.g. receptor binding activity and in vivo catabolism. This explains the significant effect of the apoE gene locus on the variability of plasma lipoprotein concentrations and moreover the implication of apoE alleles in the aetiology of multifactorial forms of hyperlipidaemia e.g. familial type III hyperlipidaemia (apoE2; arg158----cys) and polygenic hypercholesterolaemia (apoE4; cys112----arg). A further gene locus controls the concentrations in plasma of the Lp(a) lipoprotein that is composed of an LDL-like particle containing apoB-100 and the disulphide-bonded Lp(a) glycoprotein. The latter exhibits a genetic size polymorphism (MW approximately 400 kD-700 kD) that is controlled by at least seven autosomal alleles. These alleles at the same time are involved in determining the plasma concentrations of the lipoprotein that range from less than 1 mg/dl to greater than 200 mg/dl. Thus there is evidence that genetic variability in apolipoproteins relates to the variability of lipoprotein concentrations in the population and is implicated in the aetiology of multifactorial hyperlipidaemias.
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PMID:Apolipoprotein polymorphism and multifactorial hyperlipidaemia. 314 88

The body of evidence incriminating genetic factors in the etiology of CHD includes familial clustering of cases, with or without major hyperlipidemia; genetic influence on serum lipids levels in the general population; effect of genes belonging to normal polymorphisms on serum lipid levels and their variability; atherogenic effect of the genetically determined Lp(a) lipoprotein; and genetic influence on HDL apoproteins. Recent findings concerning the inherited apoE variation and genetic control of LDL cell membrane receptor activity in the general population are potentially of considerable interest. An improved understanding of the interaction between the products of "susceptibility genes" and environmental/dietary factors is important for attempts to prevent or delay the manifestations of atherosclerosis.
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PMID:The genetics of the hyperlipidemias and coronary artery disease. 716 16

Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors modulating plasma Lp(a) concentrations are poorly understood. We hypothesized that patients with hyperlipidaemia have elevated Lp(a) levels and determined the phenotype, concentration and distribution of Lp(a) in a group of hyperlipidaemic patients (n = 107) compared with a control group (n = 128). Lp(a) concentrations were significantly increased in the hyperlipidaemic patients (mean, 34 +/- 4 mg dL-1; median, 19 mg dL-1) as compared with the controls (20 +/- 3 mg dL-1; 9 mg dL-1) (P < 0.01). Interestingly, after dividing the patients into one group with elevated cholesterol (> 200 mg dL-1) (n = 44) and another group with elevated triglycerides (> 200 mg dL-1) (n = 51) we found that Lp(a) concentrations were 2.3-fold higher in the high cholesterol patients (mean, 45 +/- 5; median, 41 mg dL-1) compared to the high triglyceride subjects (20 +/- 4; 8 mg dL-1) (P < 0.01). Furthermore, a negative correlation between triglyceride and Lp(a) plasma concentrations was found in patients exhibiting triglyceride levels > 300 mg dL-1 (r = -0.41, P = 0.04, n = 36) and with triglycerides > 400 mg dL-1 (r = -0.52, P = 0.03, n = 17). These data indicate that plasma Lp(a) concentrations are elevated in hyperlipidaemia if the patients have high cholesterol levels, whereas Lp(a) is normal to low in patients with elevated triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein (a) in patients with hyperlipidaemia. 749 37

Pharmocologic treatment of the hyperlipidemia associated with the nephrotic syndrome with lovastatin has been previously shown to be safe and effective. However, there is no information on the effect of lovastatin treatment on plasma lipoprotein(a) [Lp(a)] levels in patients with the nephrotic syndrome. We administered lovastatin (40 to 80 mg/day) to 20 adult patients with unremitting nephrotic syndrome for 8 weeks to assess its effect on plasma Lp(a) and other plasma lipid concentrations. Apoprotein(a) (apo(a)) phenotype was determined in all patients. Patients were grouped according to their plasma Lp(a) levels. Those with elevated plasma Lp(a) (> or = 30 mg/dL) were placed in group I and those with normal Lp(a) levels (< 30 mg/dL) were placed in group II. Mean total cholesterol and LDL cholesterol were similarly and significantly reduced in groups I and II (-35.9% and -43.3%, P < 0.0005, P < 0.0005 group I, and -31.0% and -42.0%, P < 0.02, P < 0.03 group II, respectively). The median reduction in plasma Lp(a) was -32% (P < 0.003) in nephrotic patients in group I, whereas the median decline in plasma Lp(a) levels in nephrotic patients in group II was only -8.0% (P = 0.052). The overall frequency of the high molecular weight (M(r)) apo(a) phenotype S4 was 70% in nephrotic patients. There was no correlation between plasma Lp(a) and apo(a) phenotype. Treatment with lovastatin results in a favorable response in terms of total and low-density lipoprotein cholesterol lowering in patients with the nephrotic syndrome; however, plasma Lp(a) levels are uniformly and significantly reduced only in nephrotic patients with elevated baseline plasma Lp(a) concentrations. There was no correlation between plasma Lp(a) concentration and other lipid and biochemical parameters.
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PMID:Reduction of lipoprotein(a) following treatment with lovastatin in patients with unremitting nephrotic syndrome. 761 Dec 49

The safety and efficacy of combined bezafibrate-simvastatin therapy was evaluated in 49 patients with diet-resistant mixed hyperlipidaemia (type IIb). After a two-month placebo phase, patients were randomized to receive either Bezafibrate Slow Release (SR) 400 mg mane or simvastatin 20 mg nocte followed by three months combination therapy. Total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol were measured at monthly intervals. Apolipoproteins (apo) A1 and B, lipoprotein (a) [Lp(a)] and fibrinogen were measured before and after each treatment. Simvastatin was more effective than Bezafibrate SR in reducing total cholesterol (2.0 vs. 1.1 mmol/l, p = 0.003) and lowering LDL cholesterol (1.7 vs. 0.4 mmol/l, p = 0.0001) whereas Bezafibrate SR was more effective in reducing triglycerides (by 41% vs. 17%, p = 0.001) and fibrinogen (by 23% vs. 3%, p = 0.004). Compared with simvastatin monotherapy, combined drug therapy induced further reductions in triglycerides (by 26%, p = 0.0003) and apoB (by 11 mg/dl, p = 0.03) and an increase in apoA1 (by 21 mg/dl, p = 0.0008). Symptomatic and biochemical adverse events did not occur more frequently on combined drug therapy than on monotherapy. The combination of bezafibrate and simvastatin was more effective in controlling mixed hyperlipidaemia than either drug alone and did not provoke more adverse events.
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PMID:Combined bezafibrate and simvastatin treatment for mixed hyperlipidaemia. 764 34

Recently there has been a renewed interest in the possibility that lipoprotein(a)--Lp(a)--may be important in the pathogenesis of thrombosis-related disease. In nephrotic syndrome, hyperlipidemia is a common finding, and thrombosis is a major complication. With this regard, if Lp(a) levels increase concomitantly with low-density lipoprotein and/or very-low-density lipoprotein levels in nephrotic syndrome, this may be considered a thrombogenic factor. To probe this possibility and to corroborate the relationship between Lp(a) and fibrinolytic profiles, we measured the Lp(a) levels in patients with nephrotic syndrome (n = 43), in patients with chronic glomerulonephritis with less proteinuria than in nephrotic syndrome (n = 28), and in healthy controls (n = 50) and observed the relation between Lp(a) levels and tissue-type plasminogen activator (t-PA) activity, euglobulin fibrinolytic activity, and t-PA antigen. The Lp(a) levels were significantly higher in the patients with nephrotic syndrome as compared with both patients with chronic glomerulonephritis and healthy controls (p < 0.001). There was a direct correlation with serum cholesterol level (r = 0.780; p = 0.0001), triglyceride level (r = 0.445; p = 0.0001), and urine protein level (r = 0.675; p = 0.0001) and a reverse correlation with serum albumin levels (r = 0.566; p = 0.0001). The Lp(a) levels showed a reverse correlation with t-pA activity (r = 0.627; p = 0.0001), total fibrinolytic activity in euglobulin fraction (r = 0.458; p = 0.0001), and t-PA activity divided by the t-PA antigen (r = 0.567; p = 0.0001), but no correlation with t-PA antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein(a) levels and fibrinolytic activity in patients with nephrotic syndrome. 874 69

Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteristic of the hyperlipidemia of the nephrotic syndrome, and aggressive treatment to reduce proteinuria is mandatory.
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PMID:Accumulation of atherogenic remnants and lipoprotein(a) in the nephrotic syndrome: relation to remission of proteinuria. 776 11

This study demonstrates that peripheral apolipoprotein(a) [apo(a)] levels are higher in patients with polygenic hypercholesterolemia (PH) and combined hyperlipidemia (CH) than in controls. Levels of apo(a) inversely correlate with apo(a) isoform sizes. For a given apo(a) isoform, apo(a) levels are higher in PH and CH patients. Higher frequencies of smaller apo(a) isoforms were found in PH and CH patients than in controls, and in patients with coronary artery disease (CAD) or a family history of premature cardiovascular diseases than in patients without CAD or family history.
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PMID:Polymorphism and peripheral levels of apolipoprotein(a) in polygenic hypercholesterolemia and combined hyperlipidemia. 776 64

In normal pregnancy, all women displayed a significant elevation of serum triglyceride (TG), total cholesterol (TC), low density cholesterol (LDL-C) and high density cholesterol (HDL-C) during parturition. To study the quantitative changes in serum levels of lipids and their biological relevances during and after pregnancy, blood samples were collected from 62 normally pregnant women throughout gestation and 6 to 12 weeks postpartum. Compared with 184 nonpregnant control subjects, TG, TC, LDL-C and HDL-C were significantly elevated during the second and third trimesters of pregnancy but dropped sharply after pregnancy. To further understand the effect of pregnancy on other metabolic parameters, we compared the relative levels of apolipoproteins such as apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB), lipoprotein (a) (Lp(a)) and blood sugar during and after pregnancy. We found that apoB concentration progressively increased with advancing gestation, while the levels of apoA-I, Lp(a) and blood sugar were independent of gestation process. The physiological significance of hyperlipidemia during pregnancy is also discussed in this study.
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PMID:Alterations of serum lipid levels and their biological relevances during and after pregnancy. 779 23

We determined lipoproteins, apolipoproteins, and endothelin in 98 patients (58 female and 40 male, age 18-72 years) with hyperlipidemia (plasma cholesterol > 2.5 g/l and/or triglycerides > 2.0 g/l) and in 50 healthy subjects (20 female, 30 male, age 19-68 years). In patients with hyperlipidemia endothelin levels were elevated compared to healthy controls. Patients with plasma cholesterol above 2.5 g/l had higher endothelin and lipoprotein(a) concentrations than patients with plasma cholesterol levels less than 2.5 g/l. A positive correlation was found between the concentrations of endothelin and apolipoprotein B (r = 0.2137; P < 0.013). Smoking patients with lipoprotein (a) above 300 mg/l had higher endothelin levels than both nonsmoking patients with lipoprotein (a) above 300 mg/l and smokers with normal lipoprotein(a). In smokers endothelin correlated positively with Lp(a) (r = 0.709; P < 0.01). No correlation was found between endothelin and triglycerides nor between endothelin and age or sex. The results suggest that the vasoconstrictor endothelin contributes to the increased vasal tone in hyperlipidemia. Because endothelin also has mitogenic properties, it may play a relevant role in the development of premature atherosclerosis in patients with hyperlipidemia.
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PMID:Elevated endothelin levels in patients with hyperlipoproteinemia. 781 13


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