Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Japanese group comprising 53 hyperlipidemic and 54 normolipidemic subjects was genotyped for DNA restriction fragment length polymorphisms (RFLPs) at the apo B gene locus. The polymorphisms with XbaI and PvuII were present at allelic frequencies of 0.04 (X1 allele) and 0.96 (X2 allele), 0.94 (P1 allele) and 0.06 (P2 allele), respectively. Unlike the previous reported association of the X1 allele with hypercholesterolemia found in Caucasians there was no difference in the frequency of the X1 allele between normolipidemic and hypercholesterolemic Japanese. Among the Japanese, two RFLPs appear to be in linkage equilibrium and can be used in conjunction as a haplotype. There is no strong population association in our patient group between any allele of the RFLPs studied and hyperlipidemia.
 ...
PMID:A study of DNA polymorphism in the apolipoprotein B gene in a Japanese population. 256 22

An underlying cause of type III hyperlipoproteinemia is the presence of variant forms of apolipoprotein (apo) E that are defective in binding to apo B,E low density lipoprotein receptors. This disorder is associated almost exclusively with the apo E2/2 phenotype. However, structural and functional heterogeneity have been demonstrated within this phenotype. The apo E2(Arg158----Cys) variant, displaying 1% of normal apo E3 binding activity, is the most defective known form. In this study, we describe a method in which a pair of 19-mer synthetic oligonucleotide probes were used to distinguish between DNA coding for arginine or cysteine at position 158 in apo E. The specificity of the probes was demonstrated by using DNA from subjects whose apo E protein sequence or phenotype was known. The probes were used to screen a French-Canadian population of 34 apo E2/2 subjects to determine the frequency of the apo E2(Arg158----Cys) variant. All 34 subjects, most of whom displayed clinical or biochemical features of type III hyperlipoproteinemia, were found to be homozygous for apo E2(Arg158----Cys), strongly suggesting that this variant is the most common form of apo E2 within this ethnic and clinical population. In addition, the utility of this approach in detecting new apo E mutants was demonstrated when DNA from one of the apo E3/3 control subjects, whose family has a history of hyperlipidemia and coronary artery disease, reacted with both probes. This result suggests that this subject is heterozygous for normal apo E3 and a new apo E3 variant that is likely to be functionally equivalent to apo E2(Arg158----Cys).
 ...
PMID:Apolipoprotein E2(Arg158----Cys) frequency in a hyperlipidemic French-Canadian population of apolipoprotein E2/2 subjects. Determination by synthetic oligonucleotide probes. 291 21

Two alleles identified by DNA restriction fragment length polymorphisms around the apo A-1/C-III and insulin genes have been shown to be associated with Type IV and V hyperlipidaemia. We have genotyped 19 patients with Type III hyperlipidaemia to establish whether this association is also found in the disorder. Our data show that these associations are not responsible for the majority of cases of Type III hyperlipidaemia, but cannot exclude the possibility that a small proportion (less than 50%) of cases of Type III are caused by interaction between these alleles and the apolipoprotein E2 phenotype.
 ...
PMID:DNA polymorphisms flanking the apo A-1 and insulin genes and type III hyperlipidaemia. 298 7

We have used four independently isolated cDNA probes for human apolipoprotein B (apo B), to isolate overlapping genomic recombinants for the 3' portion of the apo B gene. The cDNA clones and a unique fragment from the genomic recombinant have been used to identify the human apo B gene in DNA from a series of rodent X human somatic cell hybrids. Our results provide evidence for the assignment of this gene to the short arm of human chromosome 2 (p23-pter). We have used the cDNA probes to identify three common DNA polymorphisms. The first, detected with the restriction enzyme XbaI and our probe pAB4, has a rare allele frequency of 0.48. The other two polymorphisms are detected with the probe pAB3. The enzyme MspI detects at least three alleles, with frequencies of 0.67, 0.16 and 0.15, while that detected with the enzyme EcoRI has a rare allele frequency of 0.12. The relative position of these polymorphisms has been mapped using the genomic recombinants. Investigation of a small number of haplotypes indicates that there is linkage equilibrium between the polymorphisms, which have a total polymorphism information content (PIC) value of more than 0.8. These polymorphisms will provide useful markers for genetic studies on chromosome 2 and for the analysis of the involvement of variants of the apo B gene in the development of hyperlipidaemia.
 ...
PMID:The isolation of genomic recombinants for the human apolipoprotein B gene and the mapping of three common DNA polymorphisms of the gene--a useful marker for human chromosome 2. 301 40

DNA probes for all eight of the major apolipoprotein genes are now available. The chromosomal location, the basic structure and in many cases the nucleotide sequences of the normal genes are known. Common DNA polymorphisms of all of the genes have been detected. These have been been used in a number of ways to investigate rare inherited defects of the apolipoprotein genes, to study the potential involvement of different variants of the genes in the development of hyperlipidaemia in patients, and to investigate the contribution of common variation in these genes in the determination of serum lipid levels in the normal population.
 ...
PMID:DNA polymorphisms of the apolipoprotein genes--their use in the investigation of the genetic component of hyperlipidaemia and atherosclerosis. 306 70

Two DNA polymorphisms adjacent to the apolipoprotein A-I/C-III and insulin genes have been suggested to be associated with hypertriglyceridemia and increased risk of coronary heart disease. Using cloned apolipoprotein A-I and insulin gene probes, we determined the genotypes of 39 subjects from six different kindreds with familial clustering of hypertriglyceridemia, 20 additional unrelated subjects with hypertriglyceridemia, 39 patients with angiographically confirmed coronary heart disease (CHD) and 61 normolipemic control subjects. The S2 allele bearing an additional SstI restriction site in the apo A-I/C-III complex was found in 16% of healthy controls, 23% of patients with CHD and 62% (P less than 0.001 when compared to controls) of unrelated subjects with hypertriglyceridemia. Among CHD patients the S2 allele was present in 6 out of 14 hypertriglyceridemic patients but only 3 out of 25 normotriglyceridemic patients (P less than 0.05). The S2 allele was present in 64% of subjects from kindreds with hypertriglyceridemia but this allele did not determine the occurrence of hyperlipidemia. The frequencies of the large size or U allele of the polymorphic DNA region flanking the 5' end of the insulin gene in CHD patients (33%) and in controls (24%) were not significantly different. Neither of the polymorphisms studied was associated with changes in serum LDL or HDL cholesterol levels in patients with CHD or unrelated subjects with hypertriglyceridemia. The data suggest that, at least in the Finnish population, the S2 allele of the apolipoprotein A-I/C-III gene complex may serve as a genetic marker for hypertriglyceridemia, whereas both DNA polymorphisms studied are probably useless in determining individual risks of atherosclerosis.
 ...
PMID:DNA polymorphisms of apolipoprotein A-I/C-III and insulin genes in familial hypertriglyceridemia and coronary heart disease. 311 75

Tumor growth and the incorporation of [3H]thymidine into tumor DNA in vivo are increased about 3 times in adult rats (greater than 250 g) after 1 to 2 days of starvation or the induction of diabetes with streptozotocin. These tumor growth responses require hyperlipemia and are reversed by refeeding or insulin treatment, respectively. They do not occur in young tumor-bearing rats (less than about 150 g) that lack appreciable fat stores. A direct relationship between the increased rates of both [3H]thymidine incorporation and tumor growth and host hyperlipemia suggests that tumor cell renewal in vivo in fed rats is limited by substances that are present in hyperlipemic blood. In this study we used a procedure for perfusion of solid tumors in situ to measure the sensitivity of tumor [3H]thymidine incorporation to hyperlipemic blood and to identify the rate-limiting substances. Tissue-isolated Morris hepatomas (7288CTC) growing in young or adult Buffalo rats were perfused with blood from donor rats. Hyperlipemic blood for perfusion was obtained from 2-day starved tumor-bearing (Buffalo) or non-tumor-bearing (Buffalo or Lewis) rats. At the end of the perfusions the tumors were labeled with a pulse of [3H]thymidine (2 microCi/g estimated tumor wet weight). [3H]Thymidine incorporation in tumors growing in fed adult rats was increased from 80 +/- 5 (SD) dpm/micrograms DNA at zero time (before perfusion) to 209 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Tumors growing in fed or starved young rats showed similar responses, and hyperlipemic blood from non-tumor-bearing rats was as effective as hyperlipemic blood from tumor-bearing rats. Perfusion of tumors growing in starved rats with normolipemic blood from fed adult rats decreased [3H]thymidine incorporation from 211 +/- 13 dpm/micrograms DNA before perfusion to 68 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Cells, plasma, and plasma subfractions from hyperlipemic blood were reconstituted to whole blood using plasma, cells, and whole blood, respectively, from fed rats and the mixtures were perfused into tumors growing in fed adult rats. Mixtures containing hyperlipemic plasma, lipid extracts (ethanol:acetone, 1:1) of hyperlipemic plasma, or albumin from hyperlipemic plasma increased tumor [3H]thymidine incorporation. Free fatty acid concentrations were increased about five times in hyperlipemic plasma and perfusion of tumors with normolipemic blood containing added linoleic and arachidonic acids increased [3H]thymidine incorporation. Blood mixtures containing palmitic, stearic, and oleic acids were inactive.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Identification of linoleic and arachidonic acids as the factors in hyperlipemic blood that increase [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ. 313 Jan 86

Different segments of the aorta and its branches show differing susceptibilities to atherosclerosis. To identify metabolic features that may account for plaque formation and sparing, we studied aortic wall respiration and glycolysis proximal and distal to an aortic coarctation in 30 rabbits fed a standard or atherogenic diet. Three months after coarctation, blood pressure in the proximal aorta was elevated, and plaque occupied 98% +/- 28% of the intimal surface compared with 57% +/- 26% for control animals (p less than 0.05). Aortic pressure distal to the stenosis remained normal, but plaque formation was markedly decreased (5% +/- 4%) compared with controls (30% +/- 27%, p less than 0.05). Metabolic studies included measurement of oxygen consumption of proximal and distal aortic walls, lactic acid production, and 2-deoxyglucose uptake. Elevated pressure or hyperlipidemia increased respiration (22.6 +/- 4.0 or 16.3 +/- 6.0 pmol oxygen consumed/min/microgram deoxyribonucleic acid [DNA] vs 5.8 +/- 5.2 for controls; p values less than 0.05) without increasing glycolytic metabolism. The coexistence of hypertension and hyperlipidemia resulted in maximal plaque formation and a sevenfold increase in both oxidative metabolism (46.6 +/- 27.2 pmol oxygen consumed/min/microgram DNA vs 5.8 +/- 5.2 for controls, p less than 0.004) and glycolytic metabolism (44 +/- 10 ng lactic acid produced/90 min/microgram DNA vs 6 +/- 3 for controls, p less than 0.004). In the spared aortic segment distal to coarctation, glycolytic metabolism was increased (10 +/- 8 ng lactic acid produced/90 min/microgram DNA vs 2 +/- 1 for controls, p less than 0.05) but oxidative metabolism remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Aortic wall metabolism in relation to susceptibility and resistance to experimental atherosclerosis. 336 36

The rate of tumor growth in vivo in adult rats (250- to 350-g total body weight) is stimulated during an acute fast. No tumor growth stimulation is observed in fasted immature rats (less than about 200-g total body weight). The different tumor growth responses in rats of these two age groups appear to depend on the increased availability to the tumor of nutrients from host fat stores in adult rats. Immature rats, which lack significant fat stores, show neither hyperlipemia nor ketosis during fasting. These experiments were performed to determine the relationship between blood fat store-derived nutrient concentrations and the onset of stimulated tumor growth in fasted adult rats. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fast. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Mobilization of host fat stores leading to increased blood concentrations of free fatty acids, glycerol, ketone bodies, and triglycerides started about 7 h after food was removed and reached its maximum after about 15 h. Increased rates of tumor growth and incorporation of thymidine into tumor DNA correlated closely with the higher circulating nutrient concentrations. Both the nutrient concentrations and tumor growth were decreased by refeeding. These findings suggest that the availability of nutrients derived from host fat stores may be rate limiting for tumor growth in vivo.
 ...
PMID:Blood nutrient concentrations and tumor growth in vivo in rats: relationships during the onset of an acute fast. 380 90

We have used a cDNA clone for human apolipoprotein CII (apo CII) to detect a common DNA polymorphism with the enzyme TaqI. This polymorphism is probably caused by a single base change approximately 2000 base-pairs from the 3' end of the structural gene. In the normal population (n = 90) the frequency of the less common allele is approximately 0.44. No significant differences were observed in the allele frequency in individuals with type IIa, IIb, III, IV and V lipoprotein patterns. There does not seem to be any population association between the TaqI polymorphism and factors that predispose an individual to hyperlipidaemia.
 ...
PMID:A DNA polymorphism adjacent to the human apolipoprotein CII gene. 609 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>