Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.

Lusis, Aldons J.; Heinzmann, C.; Sparkes, Robert S.; Scott, James; Knott, T J; Geller, Robin L.; Sparkes, Maryellen C.; Mohandas, T.

doi:10.1073/pnas.83.11.3929

Cited by 88 publications

(39 citation statements)

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“…1 The LDL receptor gene is located on the short arm of chromosome 19, where it is linked to the gene for apo E, apo C-I, and apo C-II. 39 The receptor molecule is a single-chain glycoprotein of 839 amino acids. 1 According to the functional phenotype of the mutant protein, four different classes of mutations at the LDL receptor locus have been identified.…”

Section: Discussionmentioning

confidence: 99%

Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia.

Gylling

Aalto‐Setälä

Kontula

et al. 1991

Arterioscler Thromb

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The aim of the present study was to evaluate the effect of variation of different gene loci separately and in concert on lipid metabolism in heterozygous familial hypercholesterolemia (FH). We assayed a unique low density lipoprotein (LDL) receptor gene defect (designated as FH-Helsinki), the Xba I polymorphism of the apolipoprotein (apo) B, phenotypes of the apo E, and determined the levels of serum lipoproteins, the efficiency of cholesterol absorption, and the values for several parameters of cholesterol metabolism in 51 unrelated patients with heterozygous FH. The genetic parameters were distributed independently of each other. Gender distribution and the prevalence of coronary artery disease were similar in the different apo E phenotypes, in the apo B genotypes, and in patients with and without the FH-Helsinki mutation. However, the FH-Helsinki mutation was associated with an increased body mass index. Serum LDL cholesterol was significantly elevated in patients with the FH-Helsinki mutation and the apo BX2 allele. Apo E phenotypes were not related to serum lipids per se, but the highest serum LDL cholesterol levels were measured in patients with the FH-Helsinki gene, apo E4 phenotype, and at least one X2 allele. Patients with the FH-Helsinki mutation and apo E4 phenotype had the highest cholesterol absorption efficiency. Cholesterol absorption was not related to serum lipids or lipoproteins, but LDL cholesterol was most elevated in patients with the most efficient cholesterol absorption. We conclude that in FH, diverse genetic factors exert individual and additive influences on serum LDL cholesterol levels. (Arteriosclerosis and Thrombosis 1991;11:1368-1375) S everal genetic factors contribute to the regulation of serum cholesterol level in humans. Familial hypercholesterolemia (FH) is among the best-characterized entities of the genetic abnor-

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Section: Discussionmentioning

confidence: 99%

Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia.

Gylling

Aalto‐Setälä

Kontula

et al. 1991

Arterioscler Thromb

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“…19 " 22 The potential for coordinate regulation of this gene complex is currently under investigation in a number of laboratories. The apo E gene organization 23 ' 24 is similar to that reported for other apolipoprotein genes, with the exception of the apo B gene.…”

Section: Molecular Biology Of Apo Ementioning

confidence: 99%

Apolipoprotein E polymorphism and atherosclerosis.

1988

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Lipoproteins play a central role in the development of atherosclerotic cardiovascular disease in humans. The plasma concentrations of lipoproteins and their metabolic fates are modulated by apolipoproteins on the surface of these lipid-rich particles. The hypothesis has been raised that genetic variation in apolipoproteins is a major determinant of the interindividual variation in susceptibility to coronary artery disease (CAD). In humans, the structural gene locus for plasma apolipoprotein E (apo E) is polymorphic:1 " 6 three common alleles, designated e4, e3, and e2, code for three major apo E isoforms in plasma, respectively designated apo E4, apo E3, and apo E2. Apo E is a key protein in the modulation of the metabolism of the highly atherogenic apo B-containing lipoproteins. Therefore, apo E provides a good model to test the above hypothesis.The existence of a polymorphism for such an important apolipoprotein has been a source of major interest in recent years and has raised many questions for clinicians, epidemiologists, geneticists, and biochemists. The similarities of the relative frequencies of the three common alleles among populations representing very different ethnic, cultural, and geographic settings; their different effects on •lipoprotein metabolism; and their association with certain lipid transport disorders have stimulated research aimed at a better understanding of their role in health and disease. A wealth of information 7 " 18 has accrued from studies on apolipoprotein E structure, metabolism, and function. These have considerably advanced our knowledge of the role of apo E in normal and abnormal lipoprotein metabolism, the complex interactions leading to hyperfipidemia and atherosclerosis, and the pathogenesis of type III hyperiipoproteinemia. Of major interest is the observation that the protein products of the e4 and E2 alleles have separate, and in some circumstances opposite, influences on plasma lipo- protein concentrations, a finding which leads to the hypothesis that the apo E polymorphism ranks among the major factors involved in determining interindividual differences in the initiation and progression of atherosclerosis. The evidence associating the apo E polymorphism with altered lipid and lipoprotein levels and atherosclerosis will be reviewed here. First, the apo E gene and gene product will be considered with a brief overview of molecular biology, protein chemistry, and methods for phenotyping. Second, the impact of variation at the apo E locus on plasma lipids and lipoproteins in health and disease will be discussed. Third, the metabolic interactions accounting for the various effects of the different alleles on lipids and lipoproteins will be considered to provide a unifying interpretation as to how apo E modulates the metabolism of apo B-containing lipoproteins and their remnants. Last, direct evidence associating the apo E polymorphism and atherosclerosis will be reviewed and discussed. This review is not intended to be all-inclusive, and the reader is referred to recent r...

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“…It is 3.7 Kb in length and contains four exons and three introns [8]. Three major apolipoprotein E isoforms are coded for by three alleles at the apo E locus, designated e2, e3, and e4.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E genotypes and their relation to lipid levels in a rural South African population 1

Masemola

Alberts

Urdal

2007

Scand J Public Health

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Aims: Genetic variation at the apolipoprotein E (apoE) locus is an important determinant of plasma lipids. The aim of the present study was to evaluate the association between apolipoprotein E genotype and plasma lipid levels among a rural black population in South Africa. Methods: Lipid levels and apoE genotypes were studied in 505 volunteer subjects (363 women, 142 men) resident in the Dikgale demographic surveillance site. Results: Allele frequencies were found to be 0.190 for e2, 0.518 for e3, and 0.293 for e4, indicating a relatively low frequency of the e3 allele and a high frequency of the e4 allele. To determine the effect of apoE polymorphism on lipid levels three groups were formed: namely e2-, e3-, and e4-expressing groups. A significant effect of the apoE genotype on total cholesterol, low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C)/Total cholesterol (TC) ratio, and triglycerides was observed. LDL-C was significantly lower and the HDL-C/TC ratio was significantly higher in the e2 group compared with the e3 and e4 groups. Triglyceride levels were significantly higher in the e2 group than in the e3 group. Conclusions: With the unfavourable apoE allele distribution, and the lifestyle changes taking place in rural South African populations, preventive strategies need to be developed to limit a potential epidemic of cardiovascular disease in the black population of South Africa.

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Regional mapping of human chromosome 19: organization of genes for plasma lipid transport (APOC1, -C2, and -E and LDLR) and the genes C3, PEPD, and GPI.

Cited by 88 publications

References 50 publications

Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia.

Serum low density lipoprotein cholesterol level and cholesterol absorption efficiency are influenced by apolipoprotein B and E polymorphism and by the FH-Helsinki mutation of the low density lipoprotein receptor gene in familial hypercholesterolemia.

Apolipoprotein E polymorphism and atherosclerosis.

Apolipoprotein E genotypes and their relation to lipid levels in a rural South African population 1

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