Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The content and percent composition of cholesterol, triglyceride, phospholipids, and total proteins in HDL-2 and HDL-3 were quantitated in 5 women with familial hyperalphalipoproteinemia to determine if there are any distinctive characteristics of the high density lipoproteins in this heritable disorder. The 5 women with familial hyperalphalipoproteinemia (FHA) were compared to 4 normal women, with the groups being comparable in regards to age (40 +/- 3 and 37 +/- 5 years), total plasma cholesterol (202 +/- 9 and 188 +/- 16 mg/100 ml), triglyceride (75 +/- 12 and 95 +/- 19), and differing in levels of high density lipoprotein cholesterol (C-HDL, 84 +/- 6 and 61 +/- 3 mg/100 ml) respectively. Total cholesterol in the HDL-2 and HDL-3 fractions obtained by ultracentrifugation were 43.2 +/- 3.3 and 33.8 +/- 4.1 in FHA subjects, higher than total cholesterol in HDL-2 and HDL-3 in normals, 25.8 +/- 6.2 and 21.5 +/- 1.3 mg/100 ml, P less than 0.025. Total concentration of HDL-3 was higher in FHA than in normal subjects, respectively 222.4 +/- 22.6 and 149 +/- 7.2 mg/100 ml, P less than 0.025. Lipid-protein percent composition of HDL-2 and HDL-3 in FHA and normals was nearly identical, and polyacrylamide gel electrophoresis revealed no qualitative differences in band migration and appearance of the HDL-2 and HDL-3 fractions in normal and FHA subjects. In these women with FHA, there appears to be an increased concentration of normal HDL-2 and HDL-3.
Atherosclerosis 1976 Oct
PMID:Composition of HDL-2 and HDL-3 in familial hyperalphalipoproteinemia. 18 77

Familial defective apolipoprotein B-100 is a recently identified, dominantly inherited genetic disorder caused by a G to A mutation in exon 26 of the apolipoprotein B gene. This creates a substitution of glutamine for arginine in the codon for amino acid 3500 and results in reduced affinity of low density lipoprotein (LDL) to the LDL receptor. We have integrated already published data with hitherto unpublished data from 8 countries and a total of 135 affected individuals from 56 families, in an attempt to focus on the range of expression of this mutation on lipid and lipoprotein levels and on coronary artery disease. The frequency of this mutation may be as high as 1 in 500 to 1 in 700 in Europe and in North America. The vast majority of affected heterozygotes have total and LDL cholesterol levels well above the 95th centile for age and gender; in contrast, high density lipoprotein cholesterol, very low density lipoprotein cholesterol and plasma triglycerides are not affected by the mutation. The risk of premature coronary artery disease in the carriers of the mutation is increased to levels as high as those seen in patients with clinical familial hypercholesterolemia; at age 50, about 40% of males and 20% of females heterozygous for the mutation have developed coronary artery disease. Familial defective apolipoprotein B-100 is thus a significant cause of hypercholesterolemia and premature coronary artery disease in Western societies.
Atherosclerosis 1992 Oct
PMID:Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease. 146 57

Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine (3500)----glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine(3500)----glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine(3500)----glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to "classic" familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor-defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100.
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PMID:Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia. 160 Mar 34

Familial defective apolipoprotein B100 (FDB) is a recently identified dominantly inherited genetic disorder, which is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor. FDB is caused by a G to A mutation at nucleotide 10 708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To determine the consequences of the arginine(3500)----glutamine mutation on plasma lipid levels and other clinical features, we have investigated 54 FDB heterozygotes from Germany (24 men, 30 women, mean age 37.2 (4-73) years). The average total cholesterol level in plasma was 308 mg/dl (average LDL-cholesterol 242 mg/dl), which was 116 mg/dl (120 mg/dl) above the 50th percentile of the age and sex-matched controls reported in the LRC population studies (Lipid Research Clinics' Program 1980). Tendon xanthoma and arcus lipoides were present in 25.9% and 22.2% of the patients, respectively. Plaques in the carotid arteries, determined by duplex scanning, were present in 38.9%, and coronary artery disease was present in 22.2%. This study shows that the combination of tendon xanthoma, arcus lipoides and premature atherosclerosis is no longer totally appropriate for the diagnosis of familial hypercholesterolemia (FH). It rather seems that these features are characteristic of a defective LDL receptor pathway, which could be caused by a defective LDL receptor or a defective ligand apo B100. The distinction between FH and FDB may have therapeutic implications, because certain lipid lowering drugs act by stimulation of the LDL receptor, which has a normal function in FDB.
Atherosclerosis 1992 Feb
PMID:Familial defective apolipoprotein B100: clinical characteristics of 54 cases. 163 51

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
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PMID:Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease. 166 3

The Watanabe Heritable Hyperlipidemic (WHHL) rabbit is a widely studied animal model for the human genetic disorder familial hypercholesterolemia, and spontaneously develops atherosclerotic disease. We studied the growth characteristics of cultured vascular smooth muscle cells (VSMC) from WHHL rabbits compared with VSMC from Japanese white rabbits. We measured cell proliferation, DNA synthesis, and c-myc proto-oncogene expression, in response to growth stimuli such as fetal bovine serum (FBS) and platelet-derived growth factor (PDGF). VSMC from Japanese white rabbits exhibited a 4-fold increase in cell numbers during a 5-day incubation period compared with those from WHHL rabbits. FBS and PDGF stimulated DNA synthesis, as measured by thymidine incorporation into VSMC, in both Japanese white rabbits and WHHL rabbits, however the response was significantly higher in the former strain. The intracellular pH value of VSMC determined using the pH-sensitive fluorescence dye 2',7'-bis-carboxyethyl-carboxyfluorescein was significantly higher in WHHL rabbits than in Japanese white rabbits. Proto-oncogene c-myc was induced by exposure of VSMC to FBS, however there was no significant difference in c-myc mRNA levels between the two strains. These results suggest that VSMC from WHHL rabbits are not genetically growth accelerated, but show decreased growth response to growth stimuli.
Atherosclerosis 1991 Oct
PMID:Vascular smooth muscle cells from genetically hyperlipidemic rabbit (WHHL rabbit) exhibit decreased growth response. 175 82

Homozygous familial hypercholesterolemia (FH) is a genetic disorder featuring a functional defect in cellular LDL receptors, marked elevation in circulating LDL concentrations, and premature atherosclerosis. The potential atherogenic role of apo B-containing lipoproteins other than LDL in this disease is indeterminate. We describe the quantitative and qualitative characteristics of Lp(a) as a function of apo(a) phenotype in a group of eight, unrelated homozygous FH patients. Plasma Lp(a) levels were significantly elevated (2.5-fold; mean 50 +/- 32 mg/dl) as compared to those in healthy subjects. The S2 isoform of apo(a) occurred most frequently (6 of eight patients); the rare B isoform presented in three patients. Plasma Lp(a) levels in homozygous FH did not correspond to those predicted by apo(a) phenotype. Analyses of the density distribution of Lp(a) and of Lp(a) particle size and heterogeneity as a function of density did not reveal any anomalies characteristic of homozygous FH. However, comparison of the hydrated density of Lp(a) particles as a function of apo(a) isoform content revealed a clear influence of isoform on this parameter; thus, in a B/S2 heterozygous patient, the density distribution of Lp(a) fractions containing isoform B alone, B and S2, and S2 alone, demonstrated that the apparent molecular weight of apo(a) plays a determining role in controlling the hydrated density and size of the resulting Lp(a) particle. Indeed, patients expressing the high molecular weight, S2 isoform uniformly displayed a dense form of Lp(a) (hydrated density approximately 1.055 g/ml). In subjects presenting two apo(a) isoforms, each isoform resided on distinct lipoprotein particles; in such cases, the plasma levels of the denser isoform predominated, suggesting differences in rates of formation, or rates of tissular catabolism, or in the plasma stability of the particles, or a combination of these mechanisms. Considered together, our data may be interpreted to suggest that the elevated circulating levels of Lp(a) in homozygous FH patients may reflect either an increased biosynthesis, or diminished catabolism via the cellular LDL receptor pathway, or a combination of both.
Atherosclerosis 1991 Jan
PMID:Lipoprotein Lp(a) in homozygous familial hypercholesterolemia: density profile, particle heterogeneity and apolipoprotein(a) phenotype. 182 9

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to an increased serum level of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. It is postulated that this disorder results from a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To investigate whether recurrent mutation has contributed to the high frequency of FDB, we have conducted a haplotype analysis in previously reported and newly detected FDB heterozygotes in Germany. 5 FDB families and 6 unrelated FDB heterozygotes were genotypes at 4 polymorphic sites in the 3' end of the apo B gene. These sites consisted of the diallelic markers XbaI, MspI, EcoRI and the hypervariable region (3'HVR). In 5 FDB families and 1 unrelated FDB heterozygote the arginine(3500)----glutamine mutation could be unambiguously assigned to the haplotype XbaI-/MspI+/EcoRI-/3'HVR48, in the other 5 FDB unrelated heterozygotes this finding was consistent with the combination of the genotype. The existence of the arginine(3500)----glutamine mutation on the same and supposedly rare allele suggests that the mutant alleles are identical by descent in our population. The fact that the same mutant allele was identified in North America and Austria suggests a common European origin of the arginine(3500)----glutamine mutation.
Atherosclerosis 1991 Jun
PMID:Familial defective apolipoprotein B-100: haplotype analysis of the arginine(3500)----glutamine mutation. 189 87

Dysbetalipoproteinaemia is a genetic disorder characterized by accumulation of lipoprotein remnant particles in the plasma, accelerated atherosclerosis, and the abnormal apoprotein E2. Uncontrolled diabetes mellitus can aggravate the hyperlipidaemia associated with this disorder, presumably by increasing triglyceride synthesis and reducing very low density lipoprotein catabolism by lipoprotein lipase. This report documents the gradual amelioration of dysbetalipoproteinaemia in uncontrolled diabetes mellitus following therapy with exogenous insulin alone. Although the beneficial effects of insulin therapy in this patient may include inhibition of triglyceride synthesis and improved triglyceride catabolism, we propose that insulin may also stimulate clearance of atherogenic remnant lipoprotein particles.
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PMID:Potential role of insulin in the clearance of remnant lipoproteins in dysbetalipoproteinaemia. 199 70

Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder, which leads to increased serum levels of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This genetic disorder is characterized by defective binding of the apolipoprotein B-100 (apo B-100), which is virtually the sole protein constituent of LDL, to the LDL receptor. The defective binding results from a G to A mutation at amino acid 10,708 in exon 26 of the apolipoprotein B (apo B) gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. It is postulated that FDB can exhibit the same clinical features as familial hypercholesterolemia (FH) caused by a defective LDL receptor. The purpose of this paper is to report on an individual with a defective LDL and a defective LDL receptor. The clinical features of this individual were the same as in the family members with either defective LDL or a defective LDL receptor: premature arcus lipoides, tendon xanthomata, and premature atherosclerosis. Although the clinical features were present to the same degree as in individuals with either defect the prognosis and treatment of such an individual could be different.
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PMID:Identification of a heterozygous compound individual with familial hypercholesterolemia and familial defective apolipoprotein B-100. 206 18


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