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1.
G. Feussner A. Wagner B. Kohl R. Ziegler 《Journal of molecular medicine (Berlin, Germany)》1993,71(5):362-366
Summary The clinical and biochemical characteristics of type III hyperlipoproteinemia are described in 64 patients (35 males and 29 females). Homozygosity for apolipoprotein E2, the presence of an abnormally cholesterol-rich very low density lipoprotein fraction (-VLDL) and an elevated ratio of very low density lipoprotein cholesterol to plasma triglycerides (>0.3; normal ratio about 0.2) were the basis for the diagnosis. Mean serum cholesterol and triglyceride concentrations at the first visit in the clinic were 426 ± 221 and 719 ±996 mg/dl, respectively. The mean age at diagnosis of the disorder was 49 years in males and 53 years in females. There was a high prevalence of obesity (72%), xanthomas (42%), and atherosclerosis (39%), especially peripheral vascular disease (31%). Early and correct diagnosis of this familial lipoprotein disorder seems necessary because of the prompt and beneficial response to therapeutic interventions.Abbreviations Apo
apolipoprotein
- BMI
body mass index
- CAD
coronary artery disease
- HDL
high-density lipoproteins
- HLP
hyperlipoproteinemia
- HMG CoA
3-hydroxy-3-methylglutaryl coenzyme A
- LDL
low-density lipoproteins
- Lp(a)
lipoprotein (a)
- PVD
peripheral vascular disease
- TG
triglycerides
- VLDL
very low density lipoproteins 相似文献
2.
Giso Feussner Jürgen Dobmeyer Henrik Nissen Torben Stiig Hansen 《American journal of medical genetics. Part A》1996,65(2):149-154
We report on a 20-year-old man with the combination of two independent familial lipoprotein disorders: heterozygous familial hypercholesterolemia (FH) and type III hyperlipoproteinemia (HLP). Familial hypercholesterolemia was diagnosed by elevated total and low density lipoprotein cholesterol levels and family history. By denaturing gradient gel electrophoresis, DNA sequencing and restriction fragment length polymorphism analysis, a G→A splice donor mutation in intron 3 of the proband's low density lipoprotein receptor gene was identified as the underlying molecular defect. This mutation was described previously as a receptor-negative founder mutation in Norway (FH-Elverum) and subsequently in 6 unrelated heterozygous English patients, creating a severe phenotype of familial hypercholesterolemia. Type III HLP was confirmed by homozygosity for apolipoprotein (apo) E2 and an elevated ratio of very low density lipoprotein cholesterol to serum triglycerides (0.40; normal ratio about 0.20). The patient has unusual flat xanthomas in the interdigital webs of the hands which are normally not found in either disease. These dermatological findings might therefore be indicative of the rare combination of both disorders of lipoprotein metabolism in one individual. © 1996 Wiley-Liss, Inc. 相似文献
3.
Giso Feussner Vera Feussner Michael M. Hoffmann Jens Lohrmann Heinrich Wieland Winfried Mrz 《Human mutation》1998,11(6):417-423
Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (Arg112→ Cys, Arg158→ Cys). This common apo E isoform is defective in its binding to lipoprotein receptors. However, other rare mutations in the apo ϵ gene may also, in part dominantly, predispose to the disease. In order to assess the prevalence of rare apo E variants and mutations in the apo ϵ gene in Germany, we examined apo ϵ genotypes by restriction isotyping (RI) and apo E phenotypes by isoelectric focusing (IEF) in 107 German patients with type III HLP. Concordance between apo ϵ genotype and apo E phenotype was observed in 101 subjects (94.4%). Six individuals (5.6%) had genotypes and phenotypes other than E2/2. One subject was apparently homozygous for apo E2 by IEF, but heterozygous for ϵ3/2 by RI. Sequencing of the apo ϵ gene disclosed a hitherto undescribed point mutation (TGG→ TGA) at the third position of the codon for amino acid 20 (Trp), introducing a premature termination codon. This is the first study demonstrating that in the German population type III HLP is mainly associated with homozygosity for apo E2 (Arg112→ Cys, Arg158 → Cys) and that discrepancies between apo ϵ genotype and apo E phenotype are rare in this genetic condition. Hum Mutat 11:417–423, 1998. © 1998 Wiley-Liss, Inc. 相似文献
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G. Feussner E. von Hodenberg R. Ziegler 《Journal of molecular medicine (Berlin, Germany)》1990,68(10):526-532
Summary We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.Abbreviations AIH
autoimmune hyperlipidemia
- Chol
cholesterol
- HDL
high density lipoproteins
- HLP
hyperlipoproteinemia
- HTGL
hepatic triglyceride lipase
- IDL
intermediate density lipoproteins
- IEF
isoelectric focusing
- Ig
immunoglobulin
- LDL
low density lipoproteins
- LPL
lipoprotein lipase
- PL
phospholipids
- TG
triglycerides
- VLDL
very low density lipoproteins 相似文献
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7.
Dennis Brümmer David Evans Daniela Berg Heiner Greten Ulrike Beisiegel W. A. Mann 《Journal of molecular medicine (Berlin, Germany)》1998,76(5):355-364
Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with homozygosity for the apolipoprotein (apo)
E-2 allele. Factors which may promote the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia. These
factors were investigated in eight patients with type III HLP and in nine normolipidemic controls. In vitro the interaction
of apoE with LPL was analyzed in cell binding assays. All type III HLP patients showed delayed triglyceride (TG) clearance
and remnant lipoprotein accumulation in an oral fat tolerance test. Normolipidemic apoE-2/2 controls revealed normal TG clearance
comparable to apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls. Analysis of the LPL gene revealed
an Asn 291→Ser mutation in three patients and a –93 T-G substitution combined with an Asp 9→Asn mutation in one control subject.
In addition to LPL abnormalities, postprandial hyperinsulinemia was observed in five out of eight patients. In vitro LPL compensated
the defective function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary, seven out of eight patients
with type III HLP showed LPL abnormalities and/or postprandial hyperinsulinemia. Together with the in vitro data these findings
support a coordinate effect of apoE and LPL for the manifestation of type III HLP. Hyperinsulinemia appears to be an additional
factor important for disease expression.
Received: 26 June 1997 / Accepted: 10 November 1997 相似文献
8.
J. Thiery C. Creutzfeldt W. Creutzfeldt A. K. Walli D. Seidel 《Journal of molecular medicine (Berlin, Germany)》1990,68(16):814-822
Summary We investigated long-term hypolipidemic effects and clinical safety of simvastatin, a new competitive inhibitor of 3-hydroxy-methylglutaryl coenzyme A reductase in 24 patients with familial and non-familial hypercholesterolemia. Patients received up to 40 mg simvastatin for a period of 30 months. Significant decreases were noted in plasma cholesterol (30%), plasma triglycerides (25%), very low density lipoprotein-cholesterol (26%), and low density lipoprotein-cholesterol (40%), whereas an increase in plasma high density lipoprotein-cholesterol (11%) was observed. Furthermore, the percentage decrease in plasma low density lipoprotein cholesterol was independent of individual baseline concentrations. Simvastatin did not alter the composition of low density lipoproteins or high density lipoproteins. The percentage decrease in total plasma and low density lipoprotein-cholesterol was independent of apoprotein E isoforms and low density lipoprotein-receptor activity as assayed in cultured fibroblasts. The drug therapy was well tolerated and clinical examinations revealed no adverse effects. Clinical chemistry indices and hematological, as well as endocrinological parameters remained within normal limits and ranges.Abbreviations VLDL
very low density lipoprotein
- LDL
low density lipoprotein
- HDL
high density lipoprotein
- CHD
coronary heart disease
- LDL-C
low density lipoprotein-cholesterol
- FH
familial hypercholesterolemia
- HMG-CoA
3-hydroxy-3-methylglutaryl-coenzyme A
- HELP
heparin extracorporeal low density lipoprotein precipitation
This work was supported by a grant from the Deutsche Forschungsgemeinschaft to A.K. Walli (Wa 458/I-1)Dedicated to Prof. Dr. med. F. Scheler on the occasion of his 65th birthday 相似文献
9.
Peter Henneman Femke van der Sman-de Beer Payman Hanifi Moghaddam Petra Huijts Anton FH Stalenhoef John JP Kastelein Cornelia M van Duijn Louis M Havekes Rune R Frants Ko Willems van Dijk Augustinus HM Smelt 《European journal of human genetics : EJHG》2009,17(5):620-628
Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2. 相似文献
10.
Forty-three patients with clinically and biochemically unequivocally defined type III hyperlipoproteinemia (HLP) were screened for the presence of the apolipoprotein (apo) B-100 arginine3500-->glutamine mutation. This receptor-binding defective apolipoprotein B variant is the cause of familial defective apo B-100 (FDB), an autosomal dominantly inherited disease, which leads to increased plasma cholesterol levels and premature atherosclerosis. Neither patient expressed FDB. It is concluded that the gene defect responsible for FDB is not involved in the pathogenesis of type III HLP. 相似文献
11.
Peter de Knijff Arn M. J. M. van den Maagdenberg Rune R. Frants Louis M. Havekes 《Human mutation》1994,4(3):178-194
Apolipoprotein E (apoE) is one of the major protein constituents of chylomicron and very-low-density lipoprotein (VLDL) remnants and plays a central role as a ligand in the receptor-mediated uptake of these particles by the liver. Including the most common variant, apoE3, 30 apoE variants have been characterized. At present, 14 apoE variants have been found to be associated with famiiial dysbetalipoproteinemia, a genetic lipid disorder characterized by elevated plasma cholesterol and triglyceride levels and an increased risk for atherosclerosis. Seven apoE variants were found to be associated with other forms of hyperlipoproteinemia. This report presents an overview of all currently known apoE variants and their effects on lipoprotein metabolism. © 1994 Wiley-Liss, Inc. 相似文献
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Ohmichi M Ikegami H Kurachi H Node K Morishige K Nishio Y Adachi K Matumoto K Hayakawa J Tasaka K Azuma C Murata Y 《Maturitas》2001,38(3):279-286
Objectives: Estrogen replacement therapy has favorable effects on serum lipoprotein levels in postmenopausal women with hypercholesterolemia. However, there are some patients who fail to respond to hormone replacement therapy (HRT) to lower the serum cholesterol level. In these cases, a conventional lipid-lowering therapy will be applied in addition to HRT, while the effects of these drugs are not well understood. In this study, we studied the effects of simvastatin and bezafibrate administered in addition to HRT. Methods: Patients who were hypercholesterolemic even after HRT were randomly assigned to three treatment groups: HRT only (control group, n=10), HRT+simvastatin (10 mg/day, n=10), or HRT+bezafibrate (400 mg/day, n=10). Serum lipids and lipoprotein levels were measured throughout 12 weeks. Results: The serum triglyceride levels were decreased by 24±28 and 38±13% in the HRT+simvastatin and HRT+bezafibrate groups, respectively. HRT+simvastatin decreased the total cholesterol (21±10%) and low-density lipoprotein cholesterol (28±12%) levels without affecting the high-density lipoprotein cholesterol (HDL-C) level, while HRT+bezafibrate increased the HDL-C level (12±11%). Conclusions: Treatment with simvastatin or bezafibrate in addition to HRT should be considered in cases of postmenopausal hypercholesterolemia in which HRT alone fails to lower the serum lipoprotein levels. 相似文献
15.
Treatment of patients with familial defective apolipoprotein B-100 with pravastatin and gemfibrozil: a two-period cross-over study 总被引:1,自引:0,他引:1
P. S. Hansen H. Meinertz L. U. Gerdes I. C. Klausen O. Faergeman 《Journal of molecular medicine (Berlin, Germany)》1994,72(12):1065-1070
Thirty patients with familial defective apolipoprotein B-100 were treated in a two-period (8 weeks each) cross-over study with pravastatin and gemfibrozil. Cholesterol, LDL cholesterol, and apo B were reduced by 20–25% (P < 10–4) by pravastatin and by 4–6% by gemfibrozil (pravastatin vs. gemfibrozil:P < 10–4). Response to pravastatin was variable and not correlated to gender, age, or apo E genotype. Gemfibrozil lowered triglycerides by 25% (P < 10–4) and raised HDL cholesterol by 11%. The effects of pravastatin on these two interrelated variables were significantly smaller. Both drugs increased Lp(a) significantly by about 10%. The LDL cholesterol lowering effect of pravastatin in patients with FDB is similar to that observed in patients with familial hypercholesterolemia.Abbreviations FDB
familial defective apolipoprotein B-100
- LDL
low density lipoprotein
- VLDL
very low density lipoprotein
- HDL
high density lipoprotein
- LDL-R
low density lipoprotein receptor
- HMG CoA
-hydroxy--methyl-glutaryl coenzyme A
- FH
familial hypercholesterolemia
- TG
triglycerides
- apo B
apolipoprotein B-100
- apo Al
apolipoprotein Al
- apo E
apolipoprotein E
- Lp(a)
lipoprotein(a)
- PCR
polymerase chain reaction
Correspondence to: P.S. Hansen 相似文献
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Yan'kova VI Gvozdenko TA Ivanova IL Fedoreev SA Kulesh NI 《Bulletin of experimental biology and medicine》2002,134(3):230-232
The development of type IIa alimentary hyperlipoproteinemia in rats was accompanied by changes in activity of glutathione-dependent enzymes, exhaustion of the reserves of antioxidant vitamins in the liver and blood, and intensification of lipid peroxidation. The hepatoprotective preparation Maksar obtained from far-eastern plants Maachia amurensis and containing natural biological antioxidants normalized blood lipid composition, corrected liver lipidosis, and improved the antioxidant defense system. 相似文献
18.
Shigemura K Shirakawa T Okada H Tanaka K Kamidono S Arakawa S Gotoh A 《Clinical and experimental medicine》2005,4(4):196-201
Abstract Familial hypercholesterolaemia is a genetic disorder characterised by high low-density lipoprotein (LDL) cholesterol concentrations,
which frequently gives rise to premature coronary artery disease (CAD). The clinical expression of familial hypercholesterolaemia
is highly variable even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental
and other genetic factors. Apolipoprotein E (Apo-E) has been extensively studied for its effects on the phenotype of familial
hypercholesterolaemia. In this study we examined the influence of Apo-E genotype on lipid parameters and the incidence of
CAD in 93 Greek patients with familial hypercholesterolaemia. Apo-E E2, E3 and E4 allele frequencies were 0.06, 0.86 and 0.09
respectively. The levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoproteins A and B and
lipoprotein α did not differ significantly among carriers and non-carriers of the E4 allele. The prevalence of CAD and hypertension
did not differ either. Our results suggest that the E4 allele is not associated with lipid levels or with the prevalence of
CAD among familial hypercholesterolaemia patients of the Greek population.
*The two authors were equally involved in the work 相似文献
19.
《Journal of clinical lipidology》2016,10(4):1045-1049
Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus–associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element–binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL). The non-tumor tissue had extremely low expression of low-density lipoprotein receptor and low-density lipoprotein receptor–related protein 1. Together, we speculate that marked overexpression of sterol regulatory element–binding protein-2 in the tumor may stimulate the secretion of PCSK9, which inhibits the lipoprotein receptors in the non-tumor tissue, thereby causing paraneoplastic hyperlipoproteinemia. 相似文献