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)

We have studied the frequency of DNA polymorphisms in and around the apolipoprotein A-1 (Apo-A1) and apolipoprotein CIII (Apo-CIII) gene loci in 53 persons of Caucasian descent with genetic hyperlipidemias. Three restriction-fragment-length polymorphisms (RFLPs) have previously been located 5' and 3' to the Apo-A1 gene and in the Apo-CIII gene and were detected after digestion with XmnI, PstI, and SstI, respectively, and hybridization with a 2.2-kb fragment of the Apo-A1 gene. These RFLPs are in linkage equilibrium. The rare variant sites for XmnI (X2) and SstI (S2) were more frequent in familial combined hyperlipidemia (FCH) than in controls and persons with other genetic hyperlipidemias. When considered as a haplotype, this difference was significant (P less than .03). The findings in this study suggest that the previously reported association between S2 and hypertriglyceridemia may be accounted for, in part, by inclusion of numerous patients with FCH. Our data provide further evidence that these RFLPs around and within the Apo-A1/Apo-CIII genes do not participate in unmasking clinical expression in persons with familial dysbetalipoproteinemia.
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PMID:DNA polymorphisms in and around the Apo-A1-CIII genes and genetic hyperlipidemias. 288 93

A variety of DNA markers for apolipoprotein genes were examined among patients with angiocardiographically proven heart disease and among a variety of normal individuals with various lipid values. An increased frequency of an apoAI-CIII SstI RFLP and an apoB minisatellite (allele 5) was found among patients with CHD. Higher levels of cholesterol were found among carriers of the rare apoB TaqI and the common apoCII TaqI variants, whereas higher levels of triglycerides were found in carriers of the common apoAII MspI and the rare apoB XbaI variants. Lower levels of HDL were found among carriers of the common apoAII MspI and the rare apoB PvuII variants. The biological significance of these results and those of other investigators for the pathogenesis of CHD and hyperlipidemia is suggestive but not yet fully clarified. Additional genetic epidemiologic studies and family investigations will be required. Currently used statistical methodology may lead to false inferences regarding the genetic equilibrium or disequilibrium status of closely linked DNA variants. Conclusions regarding the presence of genetic equilibrium if closely linked flanking markers are in disequilibrium may be faulty.
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PMID:Molecular genetics of apolipoproteins and coronary heart disease. 288 66

The efficacy, safety, and tolerability of simvastatin (20 mg twice a day) in the treatment of hyperlipidaemia due to unremitting nephrotic syndrome was compared with that of cholestyramine (8 g twice a day) in a crossover trial in ten patients. Two patients were taken off the protocol, one because he could not tolerate cholestyramine and one because of non-compliance with the cholestyramine regimen. No clinical or laboratory adverse experiences were noticed during the study in the other eight patients. Simvastatin was significantly more effective than cholestyramine in reducing the hyperlipidaemia--it produced a 36% decrease in total cholesterol and a 39% decrease in low density (LDL)-cholesterol, whereas cholestyramine reduced total cholesterol by 8% and LDL-cholesterol by 19%. With simvastatin the apolipoprotein B level decreased by 30%, whereas the apolipoprotein A level increased by 10%.
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PMID:Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidaemia of nephrotic syndrome. 290 53

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).
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PMID:Apolipoprotein E2(Arg158----Cys) frequency in a hyperlipidemic French-Canadian population of apolipoprotein E2/2 subjects. Determination by synthetic oligonucleotide probes. 291 21

Thirteen patients with severe acne were treated for 16 weeks with 1.0 mg/kg/day isotretinoin. There were significant increases in serum cholesterol (P less than 0.02), triglycerides (P less than 0.02) and apolipoprotein B (P less than 0.02). No changes were found in serum apolipoprotein A-1, non-esterified fatty acids (NEFA), carnitine, lactate, pyruvate, glycerol, alanine, beta-hydroxybutyrate, glucose or insulin. We therefore found no evidence that the hyperlipidaemia of isotretinoin therapy is due to increased fluxes of NEFA from adipose tissue to the liver, although we cannot exclude the possibility that there are changes in the proportion of NEFA being esterified to triglyceride or undergoing beta-oxidation. We suggest that the hyperlipidaemia induced by isotretinoin may be due to an increase in circulating lipoprotein from increased production or impaired catabolism.
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PMID:Isotretinoin and serum lipids: studies on fatty acid, apolipoprotein and intermediary metabolism. 295 78

Genetic polymorphism and rare mutants of apolipoproteins occur in humans. The polymorphism of apolipoprotein E (apoE) is controlled by three common alleles, epsilon 2, epsilon 3, and epsilon 4, which code for proteins that differ in lipoprotein receptor binding activity, or in their catabolism in vivo, or both. This may explain the observed significant effects of the apoE alleles on the phenotypic variance of plasma lipoprotein concentrations in different ethnic groups and, moreover, the involvement of apoE alleles in the pathogenesis of multifactorial forms of hyperlipidaemia, for example, hypertriglyceridaemia, familial type III hyperlipidaemia (apoE-2 Arg-158----Cys) and polygenic hypercholesterolaemia (apoE-4 Cys-112----Arg). A further polymorphic gene locus controls the concentrations of the Lp(a) lipoprotein complex in plasma, which may vary from less than 1 mg/dl to greater than 200 mg/dl between different individuals. This lipoprotein contains two different polypeptides, apoB-100 and the Lp(a) glycoprotein. The Lp(a) glycoprotein exhibits genetic polymorphism which is controlled by a series of autosomal alleles at a single locus and which is associated with lipoprotein concentrations in plasma. This suggests that the same gene locus is involved in determining Lp(a) glycoprotein phenotypes and Lp(a) lipoprotein concentrations in plasma. Thus, there is evidence that variability in apolipoprotein genes relates to the normal variance of lipoprotein concentrations in the population and that this variability is a major genetic factor in multifactorial forms of hyperlipidaemia.
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PMID:Apolipoproteins, quantitative lipoprotein traits and multifactorial hyperlipidaemia. 296

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.
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PMID:DNA polymorphisms flanking the apo A-1 and insulin genes and type III hyperlipidaemia. 298 7

Apolipoprotein (apo) E deficiency is a rare genetic disease characterized by palmar and tuberoeruptive xanthomas, type III hyperlipoproteinemia, and premature atherosclerotic vascular disease. The plasma level of apoE in apoE deficiency is less than 0.05 mg/dl by radioimmunoassay, and no structural variants of apoE were detected by immunoblot of plasma or VLDL separated by two-dimensional gel electrophoresis. The apoE gene is present in the apoE deficient patient, and there are no major insertions or deletions in the gene by Southern blot analysis. Blood monocyte-macrophages isolated from a patient with apoE deficiency contain 1-3% of the level of apoE mRNA present in monocyte-macrophages isolated from normal subjects. The apoE mRNA in the monocyte-macrophages of the apoE deficient patient is similar in size to normal apoE mRNA. The deficiency of plasma apoE in the patient with apoE deficiency is due to a markedly decreased level of apoE mRNA and decreased production of the E apolipoprotein. The decreased apoE mRNA may be due to a defect in transcription or processing of the primary transcript of the apoE gene or to instability of the apoE mRNA. The decreased plasma level of apoE results in delayed clearance of remnants of triglyceride rich lipoproteins, hyperlipidemia, and a type III phenotype.
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PMID:ApoE deficiency: markedly decreased levels of cellular ApoE mRNA. 300 75

HyperapoB, a lipoprotein phenotype characterized by increased numbers of small, dense, low-density lipoproteins (LDL), is strongly associated with coronary artery disease (CAD). Patients with hyperapoB may be normolipidemic, hypertriglyceridemic, or, when the number of LDL particles increases sufficiently, hypercholesterolemic. Concentrations of high-density lipoprotein (HDL) and its major apolipoprotein, apo A-1, are often low in plasma of patients with hyperapoB. The increased number of dense LDL in hyperapoB is due to increased LDL synthesis, secondary to increased synthesis of very-low-density lipoproteins (VLDL) and apo B. HyperapoB may be a dominant trait, although the existence of a common recessive allele at a very high frequency has not been excluded. The expression of hyperapoB appears delayed, but the phenotype is commonly found in children referred to specialty lipid clinics because of a family history of premature CAD. Published data suggest a biochemical, genetic, and metabolic relationship between hyperapoB, familial combined hyperlipidemia, and the dense LDL subclass patterns described in Mormon families. The biochemical and genetic basis for the overproduction of VLDL apo B is under further study, both molecular investigations of the apo B gene and studies of free fatty acid, triglyceride, and HDL metabolism.
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PMID:HyperapoB: a pleiotropic phenotype characterized by dense low-density lipoproteins and associated with coronary artery disease. 304 2

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.
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PMID:DNA polymorphisms of the apolipoprotein genes--their use in the investigation of the genetic component of hyperlipidaemia and atherosclerosis. 306 70


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