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)

Familial combined hyperlipidemia (FCHL) appears to be the most common, simply inherited hyperlipidemia strongly associated with coronary heart disease. In the family examined in this study, two of the siblings who met diagnostic criteria for FCHL had extensive clinical atherosclerosis before age 30, unusually premature for this form of hyperlipidemia. Lipoproteins and low-density lipoprotein (LDL) apolipoprotein (apo) B metabolism were characterized in these siblings in an attempt to gain insight into the cause of the rapid atherosclerosis in the two siblings so affected. LDL apo B production rates were very high in all three siblings (25 to 30 mg/kg/d), consistent with FCHL. beta-Very-low-density lipoprotein-beta (beta-VLDL) was present in the plasma of both siblings with accelerated atherosclerosis. The isoapolipoprotein E pattern in both of these siblings was E-3/E-2. In the third sibling, who was free of premature clinical atherosclerosis and lacked plasma beta-VLDL, the pattern was E-3/E-3. Thus, the heterozygote apo E-3/E-2 pattern may be related to the accumulation of beta-VLDL in persons with a very high apo B production rate. The abnormal accumulation of beta-VLDL may be one of the possible explanations for the rapid, premature atherosclerosis in the two siblings with FCHL in this kindred. Both male members in this kindred also had low levels of high-density lipoproteins, and thus may have had an additional risk of developing atherosclerosis due to this lipoprotein abnormality as well.
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PMID:Metabolism of apolipoprotein B in members of a family with accelerated atherosclerosis: influence of apolipoprotein E-3/E-2 pattern. 154 61

This is a report of a case of glomerular lipidosis with familial combined hyperlipidemia and panhypopituitarism. A 60-yr-old woman was admitted for evaluation of hyponatremia. Administration of hydrocortisone normalized the level of serum Na. A pituitary hormone-stimulating test and brain computed tomography revealed panhypopituitarism with an empty sella. Glucocorticoid deficiency due to secondary hypoaldosteronism was thought to have caused the Na loss. She had been treated for thyroid dysfunction and hyperlipidemia with replacement of thyroid hormone and a lipid-lowering drug. Hyperlipidemia changed from type V into IIa in 4 yr. Furthermore, one of her brothers and one of her sons were suspected to have type IV hyperlipidemia. Familial combined hyperlipidemia accompanied by secondary hypothyroidism was thought to have increased the levels of both total cholesterol and triglyceride. Two renal biopsies in 3 yr showed lipid deposits in the mesangial cells and indicated a positive correlation between the levels of serum lipids and lipid deposits in glomeruli, which suggested an important role of abnormal lipid metabolism in the progression of glomerular lipidosis.
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PMID:A case of glomerular lipidosis accompanied by familial combined hyperlipidemia and panhypopituitarism. 156 42

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

Familial combined hyperlipidemia (FCHL) is the most common genetic form of hyperlipidemia in which affected individuals manifest multiple lipoprotein phenotypes. Although the molecular defect is still unknown, several kinetic studies have demonstrated increased turnover rates of apolipoprotein B (apo B) in patients with FCHL, irrespective of their lipoprotein phenotype. Using 3 restriction fragment length polymorphisms (RFLPs) of the apo B gene (XbaI, MspI and EcoRI) we have investigated 33 families which fulfill the diagnostic criteria of FCHL. No significant difference in allele frequency was found between 33 unrelated individuals with FCHL and 107 normolipidemic controls. 3-RFLP haplotypes were constructed in each pedigree. A co-segregation analysis was performed in 7 informative families. In no family was co-segregation observed between the haplotype of the apo B gene and the phenotype of FCHL. These data are not compatible with the hypothesis that FCHL is caused by mutations of the apo B gene acting as a simple mendelian trait.
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PMID:Genetic evidence from 7 families that the apolipoprotein B gene is not involved in familial combined hyperlipidemia. 197 79

Familial combined hyperlipidemia (FCHL) is a dominantly inherited hyperlipidemia that occurs in at least 1% of the adult population and is responsible for 10% of premature coronary artery disease. In families referred for evaluation because of primary hyperlipidemia in a child, FCHL is expressed three times more commonly than familial hypercholesterolemia and half of the siblings are affected. Several metabolic defects apparently are associated with the FCHL phenotype. Most commonly, excess production of very low density lipoprotein apolipoprotein B can be demonstrated. In other families, reduced lipoprotein lipase activity is associated. One allele at a locus influencing apolipoprotein B levels predicts FCHL in a large proportion of families ascertained through affected children. Whether this allele is responsible for the excess of very low density lipoprotein apolipoprotein B detected in metabolic studies has not been elucidated. Management of FCHL in children begins with dietary modification. A bile acid sequestrant may be considered as well if diet cannot reduce the plasma low-density lipoprotein cholesterol level to less than 4.13 mmol/L (160 mg/dl) after the age of 10 years. Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors are not currently recommended for children younger than 19 years of age, we speculate that they will be increasingly utilized for the management of FCHL in teenage boys who continue to have low density lipoprotein cholesterol levels greater than 4.13 mmol/L (160 mg/dl) after dietary modification.
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PMID:Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management. 834 11

Secondary hyperlipoproteinemias are found in connection with other primary organic diseases. Typical examples are those seen with diabetes mellitus, liver and kidney diseases. In addition there are changes induced by hormonal dysfunctions such as hypothyroidism, by the use of oral contraceptives or in postmenopausal women. During pregnancy there is a physiological transient increase in lipoproteins. In addition to primary organic diseases there are a number of exogenous factors such as obesity, malnutrition and alcohol abuse causing hyperlipidemia. The relation between hypertension and hyperlipidemia described as familial dyslipidemic hypertension is less well known. Obesity, hypertension, dyslipidemia, hyperuricemia and impaired glucose tolerance are the basic conditions of the metabolic syndrome. Familial combined hyperlipidemia is a genetically determined, dyslipidemic syndrome with a high prevalence among patients with coronary artery disease and stroke. As there are some links between familial combined hyperlipidemia and secondary hyperlipoproteinemias, this disease entity is discussed together in this paper. Familial combined hyperlipidemia is metabolically, genetically and by this on a molecular level closely linked to familial dyslipidemic hypertension as well as the metabolic syndrome. The exact mechanism of this disease is currently unknown.
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PMID:[Secondary disorders of lipid metabolism, metabolic syndrome and familial combined hyperlipidemia]. 865 Sep 33

Familial combined hyperlipidemia (FCHL) is a heterogeneous disorder characterized by multiple lipoprotein phenotypes, a high risk for coronary heart disease, and predominance among the LDL fraction of smaller and denser particles. We report on an FCHL kindred (the M-kindred) in which decreased VLDL- and LDL-apoB elimination rates rather than enhanced production rates were the main kinetic abnormalities. Lipoprotein levels and metabolic parameters of all apoB-containing lipoproteins (including light and dense LDLs) were determined during placebo and pravastatin treatment periods. ApoB metabolism was studied by endogenous labeling with stable isotopes and a multicompartmental model. Five members of the M-kindred participated. The study was doubly blinded, randomized, and placebo controlled. Treatment periods of 6 weeks were separated by 2-week washout periods. All subjects had high apoB levels, 2 had a mixed lipemia, 1 had hypercholesterolemia, and 2 had hypertriglyceridemia. Familial dysbetalipoproteinemia, hypercholesterolemia, and defective apoB-100 were excluded by genetic, testing. Kinetic parameters were remarkably similar in the five study subjects during the placebo period, despite their diverse plasma lipid profiles. Compared with nine normolipidemic control subjects, low VLDL-apoB fractional catabolic rates (FCRs) (3.6 +/- .1 versus 9.3 +/- 2.9 pools per day) and low LDL-apoB FCRs (0.19 +/- 0.05 versus 0.41 +/- 0.13 pool per day) were observed in every case. The majority of the LDL particles were identified in the denser fraction (d = 1.036 to 1.063 g/mL). A clear precursor-product relationship was observed from VLDL to IDL to light LDL to dense LDL, ie, there was no "metabolic channeling." Light LDL had significantly higher FCR than dense LDL (0.82 +/- 0.21 versus 0.22 +/- 0.08 pool per day). VLDL-apoB production rates were normal (19.7 +/- 6.0 versus 21.6 +/- 6.1 mg/kg per day for control subjects). In contrast, in two subjects drawn from two other FCHL kindreds (the C- and K-kindreds), VLDL-apoB production rates were increased (35.6 and 32.1 mg/kg per day, respectively). In these two, more "typical" FCHL subjects, FCRs of LDL-apoB were near normal (0.351 and 0.311 pool per day, respectively). Pravastatin (20 mg/d) resulted in significantly lower plasma cholesterol (265 +/- 30 to 218 +/- 16 mg/dL, P < .01), LDL cholesterol (186 +/- 31 to 145 +/- 15 mg/dL, P < .03), and apoB levels (168 +/- 14 to 125 +/- 16 mg/dL, P < .01) in the five FCHL subjects of the M-kindred. No changes were observed in plasma HDL cholesterol, apoA-I, or lipoprotein(a). Pravastatin significantly increased the LDL-apoB FCR (from 0.19 +/- 0.05 to 0.34 +/- 0.04 pool per day). The FCRs of both LDL subclasses increased with treatment. No pravastatin-induced changes were seen in apoB production rates.
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PMID:A familial combined hyperlipidemic kindred with impaired apolipoprotein B catabolism. Kinetics of apolipoprotein B during placebo and pravastatin therapy. 901 40

Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, dense LDL particles that have been found to be more prone to oxidative modification. We isolated total LDL as fresh as possible from 12 normolipidemic relatives with a buoyant LDL subfraction profile (group 1), 7 normolipidemic subjects with a dense LDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a dense LDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of total LDL against Cu(2+)-oxidation in vitro. In addition, we analyzed the alpha-tocopherol and the coenzyme Q10 contents of LDL and determined their relation to LDL oxidizability. LDL isolated from group 3 subjects was more susceptible to oxidative modification than LDL from group 1 subjects (lag time: 60.4 +/- 8.1 versus 70.4 +/- 11.4 minutes; P < .05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids in LDL, together with the basal amount of dienes in LDL, were good predictors of the rate of LDL oxidation (R2 = .73, P = .0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to alpha-tocopherol in LDL were reduced compared with group 1 (P < .05). The K-value a measure of the LDL density, correlated with the the redox status (r = .37, P < .05). We conclude that in subjects with FCH total LDL is more prone to oxidation, due to the predominance of dense LDL particles. In addition, the decreased redox status of coenzyme Q10 in LDL from subjects with a dense LDL subfraction profile suggests that the LDL in the circulation has already undergone some oxidation.
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PMID:The redox status of coenzyme Q10 in total LDL as an indicator of in vivo oxidative modification. Studies on subjects with familial combined hyperlipidemia. 901 47

Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder in Western societies. In a recent report (Dallinga-Thie, G.M., X.D. Bu, M. van Linde-Sibenius Trip, J.I. Rotter, A.J. Lusis, and T.W.A. de Bruin. J. Lipid Res., 1996, 36:136-147) we have studied three restriction enzyme polymorphisms: XmnI, and MspI sites 5' of the apo AI gene and SstI site in the 3' untranslated region of exon 4 of the apo CIII gene in 18 FCH pedigrees, including 18 probands, 178 hyperlipidemic relatives, 210 normolipidemic relatives, and 176 spouses. DNA variations in the apo AI-CIII-AIV gene cluster had a modifying effect on plasma triglycerides, LDL cholesterol, and apolipoprotein CIII levels. In this study, combinations of haplotypes were analyzed to further characterize their interactions and effect on the expression of severe hyperlipidemia in FCH subjects. A specific combination of haplotypes with one chromosome carrying the X1M1S2 (1-1-2) haplotype and the other the X2M2S1 haplotype (2-2-1) was significantly more frequent in hyperlipidemic relatives (6%) than in normolipidemic relatives (3%) and spouses (0.5%). Associated with this combination of haplotypes were significantly elevated plasma cholesterol (P < 0.0001), triglycerides (P < 0.0001), and apo CIII (P < 0.001) levels when compared to the wild type combination of haplotypes 1-1-1/1-1-1. The only spouse with this specific combination of haplotypes showed a severe hyperlipidemic phenotype, similar to FCH. Furthermore, nonparametric sibpair linkage analysis revealed significant linkage between these markers in the gene cluster and the FCH phenotype (MspI P = 0.0088, SstI P = 0.044, and XMS haplotype P = 0.037). The present findings confirm that the apo AI-CIII-IV gene cluster contributes to the FCH phenotype, but this contribution is genetically complex. An epistatic interaction between different haplotypes of the gene cluster was demonstrated. The S2 allele on one haplotype was synergistic to the X2M2 allele on the other haplotype in its hyperlipidemic effect. Therefore, two different susceptibility loci exist in the gene cluster, demonstrating the paradigm of complex genetic contribution to FCH.
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PMID:Complex genetic contribution of the Apo AI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes. 906 53

Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid disorders. Resistance of adipocytes to the effects of acylation stimulating protein (ASP) may contribute to ineffective triglyceride synthesis and thereby prolonged postprandial lipemia and increased fatty acid flux to the liver seen in FCHL patients. Interestingly, ASP is identical to C3a-desArg, fragment of the third component of complement. We examined the relationships between serum levels of complement components C3 and C4 and markers of lipid and glucose metabolism in 11 large FCHL families (n = 53). Median serum C3 levels were 38% higher in affected compared to non-affected male FCHL family members (1.90 g/l vs. 1.38, P = 0.0027). The strongest correlations were observed between serum complement C3 and apolipoprotein B levels, reaching 0.77 in males. These relations were not confounded by obesity or impaired glucose tolerance. In conclusion, serum levels of the main complement components C3 and C4 correlated significantly with serum lipid levels. Further studies are needed to clarify the importance of disturbances in the complement system on the pathogenesis of FCHL and other lipid disorders.
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PMID:Serum complement and familial combined hyperlipidemia. 962 89


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