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 effects of gemfibrozil and lovastatin treatment on composition and hydrated density distribution of high-density lipoprotein (HDL) were studied in 21 patients with heterozygous familial hypercholesterolemia with the use of HDL density gradient ultracentrifugation. At baseline the patients with familial hypercholesterolemia had a markedly reduced or missing HDL2 subfraction and their HDL3 was more dense with reduced content of cholesteryl ester and increased content of triglyceride compared with HDL of control subjects with normal lipid values. Gemfibrozil and lovastatin caused primarily similar alterations in HDL components in HDL2 and HDL3 subfractions. Both agents increased apolipoprotein AI and apolipoprotein AII concentrations significantly in HDL2, whereas the apolipoprotein changes in HDL3 were relatively smaller. The difference between the effects of these two agents was related to the HDL lipid composition. Gemfibrozil increased the cholesterol concentrations of HDL2 and HDL3 (p less than 0.05 for both), and lovastatin caused significant increases in HDL2 (p less than 0.05) and HDL3 phospholipids (p less than 0.01). The observed similarity of qualitative alterations in HDL subfractions produced by these two agents in patients with familial hypercholesterolemia differs from those reported in other types of hyperlipidemia and is probably a consequence of the basic abnormalities in HDL that are characteristic of familial hypercholesterolemia.
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PMID:Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density and composition in patients with familial hypercholesterolemia. 161 16

Familial combined hyperlipidaemia (FCHL) is a common inherited disorder of lipid metabolism with a prevalence of 0.5-2.0% (refs 1, 2). It is estimated to cause 10% of premature coronary heart disease. The underlying metabolic and genetic defects in FCHL have not been identified, but a population study has suggested an association between FCHL and an XmnI restriction fragment length polymorphism (RFLP) within the apolipoprotein AI-CIII-AIV gene cluster. Here we confirm this association and show that it results from linkage disequilibrium between FCHL and the 6.6-kilobase (kb) allele of the XmnI RFLP. Subsequent analysis in seven FCHL families, ascertained through a proband carrying the 6.6 kb XmnI allele, demonstrated linkage to the AI-CIII-AIV cluster on 11q23-q24, zeta = 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.
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PMID:Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24. 167 Aug 99

Apolipoprotein B XbaI polymorphism and apolipoprotein AI/CIII SstI polymorphism have been found to be associated with variations in serum lipoprotein levels. We investigated whether these gene polymorphisms are involved in determining the lipid-modulating action of gemfibrozil. Of the 221 male subjects with hyperlipidemia studied, 121 responded well to the treatment with more than a 25% reduction in the non-high-density lipoprotein cholesterol level, whereas 100 were nonresponders. Among responders, but not nonresponders, homozygosity for the apolipoprotein B X2 allele (XbaI site present) and heterozygosity for the apolipoprotein AI/CIII S2 allele (SstI site present) were associated with elevated baseline serum low-density lipoprotein cholesterol and triglyceride levels, respectively. However, the hypolipidemic effect of gemfibrozil among the responders was independent of these gene polymorphisms. These data indicate that common polymorphisms of the apolipoprotein B and apolipoprotein AI/CIII gene loci influence serum lipid levels by mechanisms that are amenable to an intervention with gemfibrozil.
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PMID:DNA polymorphisms of apolipoprotein B and AI/CIII genes and response to gemfibrozil treatment. 167 24

The frequency of polymorphisms of the apolipoprotein (apo) B and E gene loci were studied in 59 patients with primary combined hyperlipidaemia, including 26 with familial combined hyperlipidaemia. Variation at the apo B gene locus was examined using restriction enzymes XbaI, EcoRI, and PvuII. At the apo E gene locus, variation causing the E2, E3, and E4 phenotypes was detected using the polymerase chain reaction in conjunction with allele-specific oligonucleotide probes. The frequency of apo B RFLPs in patients were not significantly different from healthy controls, however, the apo E4 allele was over-represented. This suggests that possession of the apo E4 allele may contribute to the development of the combined hyperlipidaemic phenotype and to familial combined hyperlipidaemia.
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PMID:Polymorphisms of the apolipoprotein B and E genes and their possible roles in familial and non-familial combined hyperlipidaemia. 168 59

To investigate whether increased endogenous lipogenesis contributes to elevated plasma lipid levels in individuals with apolipoprotein (apo) E2-associated hyperlipidemia (E2-HL), plasma pool cholesterol and triglyceride fatty acid syntheses were measured in subjects with E2-HL and in those with normal lipid levels. Subjects were given a priming dose of deuterium oxide (D2O) followed by maintenance doses over 48 hours. During the first 24 hours, subjects consumed prepared meals, whereas during the 24-48 hour interval, they consumed water only. Blood samples were drawn every 12 hours, and cholesterol and triglyceride fatty acid formation rates were determined from the change in deuterium enrichment. The free cholesterol fractional synthesis rate over 0-24 hours of E2-HL subjects (0.057 +/- 0.010 day-1, mean +/- SEM) was not significantly different from that of normolipidemics (0.075 +/- 0.005 day-1). Calculated cholesterol net synthesis was not different between the two groups (0.56 +/- 0.07 and 0.75 +/- 0.05 g/day, respectively). Mean free cholesterol synthesis for all subjects was higher in the fed (0-24 hour) compared with the fasted (24-48-hour) condition. Initial 12-hour triglyceride fatty acid fractional synthesis was significantly (p less than 0.01) increased in E2-HL subjects (0.143 +/- 0.012 day-1) compared with controls (0.082 +/- 0.0013 day-1). These findings suggest that in E2-HL, elevated plasma cholesterol levels are due to factors other than increased sterol synthesis, while higher de novo fatty acid synthesis contributes to the observed hypertriglyceridemia.
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PMID:Cholesterol and triglyceride fatty acid synthesis in apolipoprotein E2-associated hyperlipidemia. 173 53

The postprandial response to three test meals provided during a single day was investigated in subjects with either the apo E3/3 phenotype (n = 8), or the apo E4/3 phenotype (n = 4), who had LDL-C greater than 160 mg/dl. Vitamin A (60,000 U/m2) was ingested with the first meal and retinyl palmitate determined four hours later. Triglyceride and total cholesterol concentration were determined on whole plasma and total cholesterol and free cholesterol determined following single spin ultracentrifugation (d less than 1.006 g/ml) and dextran precipitation of the d greater than 1.006 fraction to separate apoprotein-B containing lipoproteins. Fasting values revealed significantly lower HDL-cholesterol ester (p less than 0.03) and HDL3-cholesterol ester (p less than 0.03) and significantly greater HDL-free cholesterol (p less than 0.03) and HDL3-free cholesterol (p less than 0.02) in subjects with the E4/3 phenotype. Four hour postprandial HDL and HDL3 cholesterol ester increased significantly more (p less than 0.05) in E4/3 patients and HDL and HDL3 free cholesterol decreased significantly more (p less than 0.05) in E4/3 subjects. Eight-hour postprandial change values maintained the significant HDL3-cholesterol ester and free cholesterol difference, and, revealed a significantly greater triglyceride rich lipoprotein cholesterol ester reduction (p less than 0.01) in the E4/3 group. Individuals with the apolipoprotein E4/3 phenotype reveal significant differences in postprandial lipemia compared to individuals with the E3/3 phenotype, and, postprandial lipemia following multiple meals reveals differences not apparent from responses to a single meal.
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PMID:The effect of apolipoprotein E isoform difference on postprandial lipoprotein in patients matched for triglycerides, LDL-cholesterol, and HDL-cholesterol. 175 Aug 4

Hyperlipidemia is a major risk factor for atherosclerosis and probably contributes to the increased cardiovascular mortality following renal transplantation. We studied the lipid profiles of 62 adults (29 males) with stable renal function (mean plasma creatinine 0.14 mmol/l, SD 0.07), 7 months to 21 years after renal transplantation. Fifteen patients (24%) were above the age- and sex-adjusted 95th percentile for total triglyceride and 10 (16%) for total cholesterol concentrations when compared with a local reference population. The most common lipoprotein abnormalities were type IIa (19%) and type IIb (13%). Multiple regression analysis demonstrated that the use of diuretics and angiotensin-converting enzyme inhibitors were significant factors determining plasma triglyceride concentrations. There were significant bivariate associations between plasma triglyceride concentration and duration since transplantation, plasma creatinine concentration and the use of ciclosporin and diuretics. Duration since transplantation and ciclosporin use were significant factors determining lower plasma cholesterol concentrations. The use of ciclosporin and diuretics was associated with a significantly higher apolipoprotein (apo) B concentration. The cholesterol/HDL cholesterol risk ratio correlated poorly with the apo B/apo A-1 ratio. The value of these ratios as predictors of coronary artery disease need to be established in renal transplant recipients.
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PMID:Hyperlipidemia in stable renal transplant recipients. 175 32

To determine if apolipoprotein (apo) E polymorphism influences postprandial lipemia and hence can help explain the wide range of lipemic responses to a standardized fat meal observed previously, blood samples were collected from 25 healthy men whose postprandial responses to a standardized fat meal had been measured. Venous blood samples had been obtained before the fat meal (0.73 g fat/kg containing vitamin A) and hourly thereafter for 8 hours, plasma and chylomicron triacylglyceride (TAG) concentrations had been determined, and retinyl esters (REs) in the chylomicron and nonchylomicron fractions had been measured. The original results were reanalyzed by apo E phenotype (six E2/3; 14 E3/3; four E3/4 and one E4/4, grouped as E4). Contrary to what is known about the epsilon 4 allele, the apo E4 group displayed a significantly greater response curve than did either the apo E2/3 or E3/3 groups for both plasma TAG and chylomicron RE concentrations (p less than 0.01), as reflected in a later chylomicron RE peak for the apo E4 group (p less than 0.05). The E4 group tended (p = 0.18) to have a 40% higher fasting TAG than did either of the other groups, which may reflect bias in the selection of subjects. As fasting TAG is an important determinant in postprandial lipemia, results were normalized for this variable. After adjustment, the E4 group had the lowest TAG response relative to the E3/3 group (p less than 0.01). Our findings suggest that controlling for apo E phenotype may help to reduce interindividual variation in the postprandial response to a standard fat meal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of fasting triacylglyceride concentration and apolipoprotein E polymorphism on postprandial lipemia. 193 75

A 42-year-old woman, found to have increased blood-lipid levels, developed hand-line xanthomas 3 months later. She also had an increased erythrocyte-sedimentation rate and a type lambda monoclonal IgM abnormality. In the course of the following 4 years the IgM concentration rose (from 5.8 to 12.3 g/l) steadily and synchronously with those of the triglycerides (from 147 to 391 mg/dl) and cholesterol (from 212 to 380 mg/dl). During the entire period of observation the ratio of VLDL cholesterol and triglyceride concentrations was elevated (greater than 0.4; normal: less than 0.3). Division of the lipoprotein fractions pointed to a type III hyperlipoproteinaemia. She also had an abnormality of lipid metabolism on the basis of a genetic defect (apolipoprotein-E2 homozygotism), which only manifested itself when an additional factor, IgM paraproteinaemia, was present. Paraproteins thus apparently interfered with the breakdown of the lipoproteins. Neither bezafibrate in increasing doses (200-800 mg daily) with low-fat diet nor administration of lovastatin (20 mg twice daily) together with nicotinic acid (500 mg twice daily) were adequate treatment for this form of auto-immune hyperlipidaemia.
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PMID:[Type III hyperlipoproteinemia in monoclonal IgM gammopathy]. 193 53

A family with three heterozygote and two homozygote carriers of the rare apolipoprotein E1 isoform was detected by isoelectric focusing. One of the homozygous patients had type III hyperlipidemia, while the other showed normolipemic dysbetalipoproteinemia. Restriction fragment length analysis as well as allele specific oligonucleotides were used to identify the structural alterations forming the abnormal epsilon 1 genotype. Comparison with the most common epsilon 3 allele showed that two base exchanges A for G in codon 127 and T for G in codon 158 (Asp for Gly and Cys for Arg, respectively) are responsible for the amino acid substitution which causes the charge shift observed in isoelectric focusing. The same defects have been described in the only previously characterized apoE1 (Weisgraber et al. 1984. J. Clin. Invest. 73: 1024-1033). In addition to the study by Weisgraber and coworkers, who reported on a heterozygous patient, we here describe the metabolic and clinical consequences of a homozygosity for this rare allele. Changes in lipoprotein metabolism, as well as in clinical phenotypes, were exactly identical to those seen in patients homozygous for the epsilon 2 allele, which has in common with the epsilon 1 allele the mutation in codon 158, but lacks the substitution in codon 127. In addition, lipoprotein profiles of the epsilon 3/epsilon 1 heterozygotes were indistinguishable from those of epsilon 3/epsilon 2 heterozygotes. Therefore, we conclude that the additional mutation in codon 127 that characterizes the epsilon 1 allele is of no functional importance in vivo.
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PMID:Normolipemic dysbetalipoproteinemia and hyperlipoproteinemia type III in subjects homozygous for a rare genetic apolipoprotein E variant (apoE1). 197


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