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)

The purpose of this study was to determine the effect of serum lipids, lipoprotein fractions, and apolipoprotein (apo) A-1, B and E on mortality from vascular and nonvascular causes in an unselected elderly population. The random sample of 347 community-living individuals aged 65 years or older was obtained in 1982. Serum total cholesterol, LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride, and apo A-1, B and E were determined at baseline. After the 11-year follow-up, 199 of the participants had died, and 148 were still alive. Mortality data from vascular and nonvascular causes by the end of 1993 were obtained from official registers. In the univariate analysis, a low total cholesterol level was associated with death due to both vascular and nonvascular causes (P value for trend, .021 and .0027, respectively). After the adjustment for other risk factors, the inverse association between total cholesterol and vascular mortality disappeared, but low total cholesterol was still a significant predictor of death due to nonvascular causes. Adjusted relative risks (RRs) of death due to nonvascular causes for those with elevated total cholesterol (5.1 to 6.5, 6.6 to 8.0, and > 8.0 mmol/L) compared with the reference group (< or = 5.0 mmol/L) were 0.5 (95% confidence interval [CI], 0.2 to 1.2), 0.6 (0.2 to 1.0), and 0.2 (0 to 0.8), respectively. Neither concentrations of HDL-C, LDL-C, triglyceride, nor apo B were associated with vascular or nonvascular mortality. On the other hand, low concentration of apo A-1 predicted vascular death. The RR for the lowest tertile was 1.6 (1.1 to 2.5) compared with the highest tertile. Furthermore, the occurrence of the apo E e4 allele was associated with increased risk of vascular mortality (RR, 1.5; 95% CI, 1.0 to 2.2), but the risk was not related to the levels of lipids, lipoproteins, or other apolipoproteins at baseline. Nonvascular mortality also tended to be predicted by the presence of the e4 allele (RR, 1.5; 95% CI, 0.9 to 2.5). In an unselected elderly population, the allelic variation of apo E, i.e., the presence of the e4 allele, and a low concentration of apo A-1 were more accurate indicators of vascular mortality than total cholesterol or lipoprotein fractions. The risk associated with the apo E polymorphism is unrelated to dyslipidemia.
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PMID:Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. 926 Dec 50

In vitro data suggested that albumin is a key factor controlling apolipoprotein (apo) synthesis by hepatocytes. Studies in analbuminemic rats have shown an increase in secretion of apoB-containing lipoprotein from the liver. We studied the kinetic aspects of apoB- and apoAI-containing lipoprotein metabolism in two sisters with analbuminemia using a constant 14-hour infusion of leucine labeled with stable isotopes. Compared with control subjects, total cholesterol was higher in the two patients (432 and 461 versus 155 +/- 14 mg/dL), as was apoB (257 and 230 versus 72 +/- 7 mg/dL). Triglycerides were slightly increased (134 and 105 versus 89 +/- 9 mg/dL), whereas apoAI was lower (109 and 105 versus 124 +/- 6 mg/dL). VLDL-apoB production was higher, as was the production of IDL-apoB and LDL-apoB (32.8 and 36.0 versus 24.8 +/- 5.9, 32.1 and 27.2 versus 16.4 +/- 2.3, and 14.1 and 17.6 versus 10.3 +/- 1.2 mg.kg-1.d-1, respectively). The fractional catabolic rate of all the apoB-containing lipoproteins was decreased (0.23 and 0.37 versus 0.48 +/- 0.05, 0.27 and 0.28 versus 0.62 +/- 0.08, and 0.012 and 0.009 versus 0.022 +/- 0.002.h-1, respectively). A similar mechanism could explain the dyslipidemia observed in other conditions associated with low albumin levels, such as nephrotic syndrome.
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PMID:Lipoprotein kinetics in patients with analbuminemia. Evidence for the role of serum albumin in controlling lipoprotein metabolism. 926 Dec 69

Plasma lipoproteins (LP) may be identified on the basis of density properties or apolipoprotein (apo) composition. ApoB-containing LP occur in VLDL, IDL and LDL. There are several types of apoB-containing LP characterized by specific composition of minor apolipoproteins (apoC, apoE etc.) and lipid constituents (triglycerides and cholesterol), metabolic properties and relative atherogenicity. The alterations of lipoprotein metabolism in renal disease resulting in elevated levels of apoB-containing LP may be reflected in hyperlipidemia. Whereas nephrotic syndrome and heavy proteinuria are associated with increased formation of cholesterol-rich apoB-containing LP in LDL and VLDL, the characteristic feature in renal failure is the accumulation of intact or partially metabolised triglyceride-rich LP in IDL and VLDL. The potentially atherogenic apoB-containing LP have been linked to the pathogenic processes that result in progressive glomerular and interstitial lesions and ultimate loss of renal function. The mechanisms of injury are not fully understood. Receptor- and non-receptor mediated uptake of LP by mesangial cells may induce or accelerate proliferative and sclerotic processes in the glomerular mesangium that are analogous to atherosclerosis in the arterial wall. Changes in glomerular permeability can result in increased filtration of LP that may be internalized by tubular cells and elicit corresponding lesions in the interstitial tissues. The negative impact of proteinuria on the prognosis of renal disease could be mediated in part through an increased filtration of lipoproteins. Induction of hyperlipidemia accelerates glomerular and interstitial damage in experimental renal failure. This can be attenuated by treatment with hypolipemic agents. In patients, increased concentrations of apoB-containing LP are associated with more rapid progression of renal insufficiency in both primary renal disease and diabetic nephropathy. It is, however, presently not known to what extent treatment of the renal dyslipidemia can modify the progression of chronic renal failure. Experimental and clinical evidence suggest that apoB-containing LP may play a pathogenetic role in the progression of renal disease.
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PMID:Progression of renal failure: role of apolipoprotein B-containing lipoproteins. 940 33

Studies on monozygotic twins support a role for genetic determinants of plasma lipid, lipoprotein, and apolipoprotein levels. Gene variants of the enzyme lipoprotein lipase have been shown to associate with dyslipidemia and coronary artery disease. We assessed the gene-environment interaction by investigating the relationship between the lipoprotein lipase gene and plasma lipid, lipoprotein, and apolipoprotein variability and levels among 54 male monozygotic twin pairs (aged 18-28 years). The Ser447-Ter mutation (C-->G transversion) was associated with significantly smaller within-pair differences in plasma high density lipoprotein-cholesterol (CG [n = 10] vs. CC [n = 44], 3.7+/-5.3 mg/dl vs. 6.4+/-5.2 mg/dl, P < 0.03) and total cholesterol (CG [n = 10] vs. CC [n = 44], 7.9+/-9.4 mg/dl vs. 15.8+/-12.7 mg/dl, P < 0.05), indicating attenuated variability in response to environmental stimuli. This observation of a restrictive variability gene effect further supports a role for the lipoprotein lipase gene in the genetic regulation of lipids and lipoproteins and suggests that the Ser447-Ter mutation exerts multiple effects. This study also raises the possibility of a genetically determined responsiveness to dyslipidemia therapies.
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PMID:The Ser447-Ter mutation of the lipoprotein lipase gene relates to variability of serum lipid and lipoprotein levels in monozygotic twins. 950 3

The lipid profile is known to alter in patients with infection, but there has not been a study of the apolipoprotein levels in serum of otherwise healthy children during infection. Lipids, lipoproteins, apolipoproteins A-1 and B and lipoprotein (a) were evaluated prospectively in 31 consecutive children, aged 4-15 years, who were admitted to the hospital with bacterial pharyngitis. The degree of dyslipidemia associated with bacterial pharyngitis was assessed using each child as his/her own control and by comparison with 79 healthy children who had not had an infection during the past 3 months. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B levels were significantly decreased during the symptomatic phase of the disease, whereas the serum triglyceride level was slightly elevated. Serum lipoprotein (a) concentration did not change significantly. In conclusion, it is suggested that serum lipids, lipoproteins and apolipoproteins should not be assessed during infection because of the possible transient changes of these parameters during infection or inflammation.
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PMID:Should children with infection be tested for lipid, lipoprotein and apolipoprotein? 958

We studied the allelic frequency of the variable number of tandem repeats region 3' of the apolipoprotein B gene (apoB 3' VNTR) and its impact on coronary artery disease (CAD) in 150 patients with CAD and 153 normal controls in a Taiwan population. apoB 3' VNTR alleles were classified according to the number of repeats of a 15-bp hypervariable elements (HVE), the sequence of which was determined using the polymerase chain reaction and direct sequencing. Thirteen alleles comprising from 26 to 54 HVEs were identified. The CAD patients had greater heterozygosity (0.58 vs 0.42) and a higher frequency of long (> 36-HVE) apoB 3' VNTR alleles than the controls (18.7% vs 10.8%, p < 0.01). CAD patients with two HVE-36 alleles and no HVE-32 alleles (the two most common forms) had significantly higher concentrations of LDL-cholesterol, apolipoprotein B, and triglycerides, and significantly lower values of HDL-cholesterol and apolipoprotein AI than the control group (p < 0.01 for all comparisons). The length of the apoB 3' VNTR was not correlated with the plasma concentrations of any of the lipids. We conclude that long apoB 3' VNTR alleles occur more frequently in CAD patients, but that apoB 3'VNTR genotypic variation has little impact on the risk of dyslipidemia in Taiwanese.
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PMID:Polymorphisms of the apolipoprotein B 3' variable number of tandem repeats region associated with coronary artery disease in Taiwanese. 958 73

The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted.
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PMID:Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects. 971 26

There is growing evidence of the capacity of vitamin A to regulate the expression of the genetic region that encodes apolipoproteins (apo) A-I, C-III, and A-IV. This region in turn has been proposed to modulate the expression of hyperlipidemia in the commonest genetic form of dyslipidemia, familial combined hyperlipidemia (FCHL). The hypothesis tested here was whether vitamin A (retinol), by controlling the expression of the AI-CIII-AIV gene cluster, plays a role in modulating the hyperlipidemic phenotype in FCHL. We approached the subject by studying three genetic variants of this region: a C1100-T transition in exon 3 of the apoC-III gene, a G3206-T transversion in exon 4 of the apoC-III gene, and a G-75-A substitution in the promoter region of the apoA-I gene. The association between plasma vitamin A concentrations and differences in the plasma concentrations of apolipoproteins A-I and C-III based on the different genotypes was assessed in 48 FCHL patients and 74 of their normolipidemic relatives. The results indicated that the subjects carrying genetic variants associated with increased concentrations of apoA-I and C-III (C1100-T and G-75-A) also presented increased plasma concentrations of vitamin A. This was only observed among the FCHL patients, which suggested that certain characteristics of these patients contributed to this association. The G3206-T was not associated with changes in either apolipoprotein concentrations or in vitamin A. In summary, we report a relationship between genetically determined elevations of proteins of the AI-CIII-AIV gene cluster and vitamin A in FCHL patients. More studies will be needed to confirm that vitamin A plays a role in FCHL which might also be important for its potential application to therapeutical approaches.
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PMID:Vitamin A is linked to the expression of the AI-CIII-AIV gene cluster in familial combined hyperlipidemia. 1006 30

It has been suggested that the postprandial elevation of plasma triglycerides is more closely linked to coronary heart disease (CHD) than the fasting triglyceride level. However, the postprandial situation is complex, as hepatogenous triglyceride-rich lipoprotein (TRL) particles (apolipoprotein [apo]B-100 and very-low-density lipoprotein [VLDL]) are mixed in the blood with apoB-48-containing lipoproteins secreted from the intestine. To analyze the relative proportion of liver-derived and intestinal apoB-containing TRL in subjects with and without CHD, we performed standardized oral fat-loading tests in young survivors of myocardial infarction, a large proportion of whom are hypertriglyceridemic (HTG), as well as sex- and population-matched healthy control subjects. A special effort was made to recruit healthy HTG subjects as controls for the HTG patients. Fasting plasma triglycerides (3.74+/-1.35 v3.01+/-0.83, NS), low-density lipoprotein (LDL) cholesterol, and VLDL lipids, and apoB-100 and apoB-48 content at Svedberg flotation rate (Sf) 60-400, Sf 20-60, and Sf 12-20 did not differ between HTG patients (n = 10) and HTG controls (n = 14). Normotriglyceridemic (NTG) patients (n = 15) had higher fasting plasma triglycerides (1.44+/-0.39 v 0.98+/-0.33 mmol/L, P < .05) and LDL cholesterol (4.07+/-0.71 v 3.43+/-0.64, P < .05) than NTG controls (n = 34). The triglyceride elevation was accounted for by a higher level of small VLDL (apoB-100 in the Sf 20-60 fraction, 52+/-17 v29+/-20 mg/L, P < .05). HTG patients responded with clearly elevated plasma triglycerides in the late postprandial phase, ie, 7, 8, and 9 hours after fat intake. Essentially, this was explained by a retention of large VLDL particles, since HTG patients exhibited no major differences in apoB-48 concentrations in the Sf > 400, Sf 60-400, and Sf 20-60 fractions but showed marked differences in the level of apoB-100 at Sf 60-400 (large VLDL) 9 hours after fat intake when compared with HTG controls (101+/-13 v 57+/-5 mg/L, P < .01). NTG patients were characterized by a more rapid increase of large VLDL in the early postprandial state, ie, 3 hours after fat intake, with a mean increase from baseline to 3 hours of 24.1+/-6.7 mg/L for NTG patients and 11.8+/-2.0 mg/L for controls (P < .05). ApoB-48 levels were also slightly higher, but all TRL parameters returned to baseline within 9 hours after fat intake. In conclusion, elevated triglyceride levels in the postprandial state in CHD patients are explained to a large extent by the accumulation of endogenous TRL. This suggests that the postprandial dyslipidemia encountered in CHD is more dependent on a failure of regulation of endogenous TRL versus the exogenous TRL species.
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PMID:Differences in postprandial concentrations of very-low-density lipoprotein and chylomicron remnants between normotriglyceridemic and hypertriglyceridemic men with and without coronary heart disease. 1009 4

Coronary artery disease is a leading cause of death in France. Some of its risk factors are well identified such as age, smoking, high blood pressure and dyslipidemia, but some others such as lipoprotein (a) (Lp(a)) are still under investigation. Lp(a) is an LDL-like particle to which is linked an apolipoprotein (a). The latter shows a high sequence homology with plasminogen that gives Lp(a) thrombogenic properties in addition to its atherogenic capacity. Many epidemiological studies have shown that a high plasma level of Lp(a) is a risk factor for coronary, cerebral and peripheral atherosclerosis. Out of thirteen prospective studies, ten have confirmed this result. The negative results from the three remaining studies were probably due to either the inadequate storage of the samples or the preventive drug treatment given to the patients during the studies and to the lack of standardization of Lp(a) assays. More over it has been shown that beside high plasma Lp(a) level, the presence of a low molecular weight Apo(a) isoform is also related to a higher incidence of coronary artery disease. This review of the literature clearly demonstrates the relationship between Lp(a) and atherosclerosis, and the need to measure Lp(a) in order to better evaluate the risk of atherosclerotic vascular disease especially in patients with a hyper LDLemia an early cardio- or cerebrovascular disease or a family history of atherosclerosis. Management of patients with high Lp(a) concentrations should be directed at minimizing all other risk factors for atherosclerotic disease.
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PMID:[Lipoprotein(a): risk factor for atherosclerotic vascular disease important to take into account in practice]. 1021 Jul 42


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