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)

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

It has recently been suggested that a substitution of glutamine for arginine at residue 3500 of apolipoprotein (apo) B-100 causes familial defective apo B-100 (FDB), an autosomal, dominantly inherited disorder, which leads to increased serum cholesterol levels. From a sample of 243 patients from Munich with type IIa hyperlipoproteinemia (HL), we have identified eight individuals with the apo B-100 arginine(3500)----glutamine mutation. In a group of 57 subjects with defective low density lipoprotein receptor (LDLR), no mutant apo B alleles were detected. The frequency of FDB in patients with type IIa HL was estimated to be 3%. In the kindreds of three of the probands, 10 additional carriers of the apo B mutation were identified. Clinical and biochemical data reveal a striking similarity between patients with FDB and those with a defect in the LDLR gene. Our data support previous findings that FDB is a serious disorder causing premature atherosclerosis.
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PMID:Familial defective apolipoprotein B-100. Comparison with familial hypercholesterolemia in 18 cases detected in Munich. 216 82

Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.
Atherosclerosis 1990 Jan
PMID:Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases. 231 Apr 29

Several recent reports have examined whether there is a correlation between the presence of some minor alleles of the highly polymorphic apolipoprotein B gene and atherosclerosis and premature heart disease. The present study extends this investigation. A high-resolution method was used to study the allele frequencies of a hypervariable minisatellite region close to the apolipoprotein B gene in 110 patients with severe coronary disease and in 117 normal controls. Alleles containing 38, 44, 46, or 48 hypervariable elements showed an association with coronary heart disease. These alleles were also associated with elevated serum levels of total cholesterol and apolipoprotein B among patients and with elevated serum levels of total triglycerides among controls. The hypervariable region showed strong linkage disequilibrium with a polymorphic EcoRI site in exon 29 and was in linkage equilibrium with a polymorphic MspI site in exon 26. Two patients carried a base change at codon 3500 that results in an arginine-to-glutamine substitution; the base change was linked in both instances to the allele with 48 hypervariable elements.
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PMID:Hypervariability in a minisatellite 3' of the apolipoprotein B gene in patients with coronary heart disease compared with normal controls. 235 70

Familial defective apolipoprotein B-100 is a genetic disorder which is associated with elevated plasma LDL levels. It appears to result from a G----A mutation at nucleotide 10,708 in exon 26 of the apolipoprotein B-100 gene leading to a substitution of glutamine for arginine at amino acid residue 3500. We explored the possible role of this point mutation as a cause of elevated plasma cholesterol among the Finns, a genetically isolated population in which both hypercholesterolemia and coronary heart disease are common: 552 hyperlipidemic patients from Western and Southern Finland were screened either by assaying patient sera with monoclonal antibody MB47 or by amplifying the region of the apo B gene containing the nucleotide 10,708 followed by hybridization of the amplified DNA with allele-specific oligonucleotide probes. Not a single individual with this particular mutation could be found. We conclude that familial defective apo B-100 is not a common cause of elevated plasma cholesterol in this population.
Atherosclerosis 1990 Jun
PMID:Absence of familial defective apolipoprotein B-100 in Finnish patients with elevated serum cholesterol. 237 82

A lot of over 60 atherosclerotics with clinical manifestations of senile depressive illness was studied comparatively with a lot of subjects of the same age with essential arterial hypertension (EAH). As concerns the behaviour of the catecholamine content in CSF and blood, the total catecholamines are approxiately equal in the two lots, but with a clear difference of the catecholamine fractions. The CSF catecholamines behaviour in old atherosclerotics is characterized by the presence of increased values of noradrenaline (NA) and of adrenaline (A), with increased statistical significance, but without modifications of the adrenaline percentage (A %) from the total catecholamines, comparatively to the values found in normal subjects. The serotonin (5-HT) content of the CSF in men with atherosclerotic senile depressive illness was lower even than in subjects with coronary atherosclerosis. In atherosclerosis protides modifications precede the histologic changes. In CSF, GLU, ALA, TYR increase in old subjects. In blood, GLU, ALA, TYR, HIS, LEU, SER increase in the same subjects. ARG decreases with age. THR is higher in men than in women. In the urine of all the men as well as of all the women of more than 60 years, GLN and ALA have increased values. LYS increases with age. GLN and ARG are higher in men than in women.
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PMID:Pattern of the cerebrospinal fluid (CSF) and blood biogenic amines and of the CSF, blood and urine amino acids as pathogenetic ground of the senile depressive illness. 677 91

Arginine, glutamine, the long chain polyunsaturated omega-3 and omega-6 fatty acids, and, to a lesser extent, ribonucleic acid and the vitamins E, C, and A have pharmacologic effects when given in amounts in excess of what is needed to prevent nutritional deficiency. These effects are exerted primarily via the immune system, and immunoenhancing diets that embody the recently developed principles of nutritional pharmacology have been shown to reduce infectious complications by approximately 75% in surgical patients and hospital stay by more than 20% in surgical patients and patients in the intensive care unit in three independent, prospective, randomized studies, two of which were double-blinded. These findings suggest that specialized diets can be designed that will be of benefit to patients with cancer, atherosclerosis, intestinal diseases, autoimmune diseases, infections, and trauma. However, the interaction of these nutrients in pharmacologic amounts with standard pharmacologic drugs is largely unknown, as are the effects of long-term administration of specialized diets to treat these conditions.
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PMID:Immunoenhancement via enteral nutrition. 769 65

Familial defective apolipoprotein B-100 is a newly revealed genetic disorder which leads to a rise of atherogenic LDL lipoproteins. It is probably due to the replacement of a single amino acid in the huge apoliprotein B-100 molecule, i.e. substitution of glutamine by arginine in position 3,500. Thus altered LDL-lipoproteins are unable to bind with the LDL-receptor. As a result of the mentioned metabolic disorder a slightly or markedly elevated plasma cholesterol develops which very probably leads to premature manifestation of atherosclerosis. The disease is transmitted by autosomal dominant inheritance and its incidence in the population is estimated to amount to 1:500, i.e. a similar rate as familial hypercholesterolaemia. In the submitted paper some historical facts are presented which led to the detection of the disease, methods which are used for its detection, and the author presents also results of the first, so still limited clinical investigations.
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PMID:[Familial apolipoprotein B-100 defect, a newly discovered lipid metabolism disorder]. 780 94

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder caused by the substitution of glutamine for arginine at position 3500 in apo B-100. The presence of mutant apo B-100 in low-density lipoproteins (LDL) markedly reduces their affinity for the LDL receptor, leading to hypercholesterolaemia and increased proneness to coronary artery disease. In some FDB heterozygotes the clinical picture is indistinguishable from that in heterozygous familial hypercholesterolaemia (FH). In European and N. American populations the frequency of FDB is at least as high as that of FH. In most lipid clinics, 2-5% of patients given a clinical diagnosis of FH have FDB, not FH. Most FDB heterozygotes respond well to drugs that lower plasma LDL levels by inducing receptor activity. This may be due partly to increased receptor-mediated hepatic removal of mutant and normal precursors of LDL, using apo E as recognition element. Several important lessons can be learnt from the study of FDB.
Atherosclerosis 1993 Dec
PMID:Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolaemia. 814 33

A glutamine/histidine polymorphism at residue 360 in apolipoprotein (apo) A-IV that generates two electrophoretically detectable isoforms, apo A-IV-1 and apo A-IV-2, affects the plasma concentration of lipoprotein(a) (Lp[a]) in a healthy population. To verify this unexpected association we analyzed the effect of the apo A-IV polymorphism on Lp(a) serum concentrations in 275 male coronary heart disease patients. Allele frequencies of apo A-IV-1 and apo A-IV-2 were 0.917 and 0.083, respectively. In addition, apo A-IV-1/2 heterozygotes showed a 30% lower geometric mean concentration of Lp(a) than apo A-IV-1/1 homozygotes in this study. The relative frequency of Lp(a) concentrations > 20 mg/dl was significantly increased by a factor of 2.25 in apo A-IV-1/1 homozygotes. Other lipid parameters were not significantly affected by this apo A-IV polymorphism. Because of the relations between Lp(a) and the fibrinolytic system, we also analyzed the effect of the apo A-IV polymorphism on hemostatic variables. Apo A-IV-1/2 heterozygosity was associated with a 70% higher geometric mean plasma concentration of D-dimer, i.e., proteolytic fragments of cross-linked fibrin. Plasma concentrations of prothrombin fragments F1 + F2, fibrinogen, plasminogen, and plasminogen activator inhibitor-1 were unaffected. In conclusion, our results indicate a hitherto unappreciated role of the apo A-IV gene or a closely linked locus for the regulation of Lp(a) metabolism and hemostasis and also possibly for atherosclerosis and thrombosis.
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PMID:Glutamine/histidine polymorphism in apo A-IV affects plasma concentrations of lipoprotein(a) and fibrin split products in coronary heart disease patients. 842 59


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