On Having No Beta-Lipoprotein a Syndrome Comprising a-Beta-Lipoproteinæmia, Acanthocytosis, and Steatorrhœa

Salt, H.B.; Wolff, O. H.; Lloyd, J. K.; Fosbrooke, Audrey S.; Cameron, A. H.; Hubble, Douglas

doi:10.1016/s0140-6736(60)91478-1

Cited by 335 publications

(73 citation statements)

References 17 publications

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“…5-lipoprotein), and no chylomicra were present. The lipoprotein pattern was similar to that reported by Schwartz et al (1963) and Salt et al (1960). The density gradient used was identical to that employed by Dr. K. W. Walton in investigations on the case reported by Salt and his colleagues.…”

Section: Discussionsupporting

confidence: 86%

“…Retinal changes have been observed in 6 of the 12 previously reported cases (Bassen and Kornzweig, 1950;Jampel and Falls, 1958;Kornzweig and Bassen, 1957;Druez, 1959;Friedman, Cohn, Zymaris, and Goldner, 1960;Mier, Schwartz, and Boshes, 1960) and electroretinography has been abnormal in one case in which the retinoscopy was normal (Lamy et al, 1961). The 5 patients without retinopathy were all under the age of 14 years at the time of reporting (Salt et al, 1960;Mabry et al, 1960;Wolff and Bauman, 1961;Schwartz et al, 1963;Ways et al, 1963). The patient reported on by Singer et al had no retinopathy at the age of 13 years, but at the age of 19 marked atypical retinitis pigmentosa was present (Jampel and Falls, 1958).…”

Section: Discussionmentioning

confidence: 99%

“…Where biopsy of the small intestinal mucosa has been carried out the histological appearance has always been the same. The columnar cells covering the villi have unusually clear cytoplasm (Salt et al, 1960;Mabry, Di George, and Auerbach, 1960;Lamy, Frezal, Polonovski, and Rey, 1961;Schwartz, Rowland, Eder, Marks, Osserman, Hirschberg, and Anderson, 1963;Ways, Reed, and Hanahan, 1963). The patient to be described was diagnosed at the age of 10 months and showed some unusual features that led to his early death.…”

mentioning

confidence: 99%

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A- -lipoproteinaemia (Bassen-Kornzweig Syndrome): Report of a Case

Becroft¹,

Costello²,

Scott³

1965

Archives of Disease in Childhood

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A- -lipoproteinaemia (Bassen-Kornzweig Syndrome): Report of a Case

Becroft¹,

Costello²,

Scott³

1965

Archives of Disease in Childhood

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“…However, inhibition of MTP must be quite extensive to have an effect in vivo, as obligate heterozygotes for MTP deficiency (fathers or mothers of patients with abetalipoproteinemia) have a fairly normal plasma lipid and lipoprotein pattern. 8,24,25 It is more difficult to speculate about the physiological effects of stimulated MTP function. In the present work, we describe a common variant of the MTP promoter leading to enhanced transcriptional activity of the gene.…”

Section: Discussionmentioning

confidence: 99%

A Common Functional Polymorphism in the Promoter Region of the Microsomal Triglyceride Transfer Protein Gene Influences Plasma LDL Levels

Karpe¹,

Lundahl²,

Ehrenborg³

et al. 1998

ATVB

131

140

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Abstract-Microsomal triglyceride transfer protein (MTP) is required for the assembly and cellular secretion of apolipoprotein B (apoB) -containing lipoproteins from the liver and intestine. The secretion pattern of apoB-containing lipoproteins is likely to influence the VLDL and LDL levels in plasma. By initial opportunistic screening for polymorphic sites in the regulatory region of the MTP gene by gene sequencing in 20 healthy male subjects, a common functional G/T polymorphism was detected 493 bp upstream from the transcriptional start point. There was differential binding of unique nuclear proteins at this site, as shown by electrophoretic mobility shift assay. The G variant seemed to bind two or three nuclear proteins that do not bind to the T variant. Expression studies with minimal promoter constructs linked to the chloramphenicol acetyltransferase reporter and transfected into HepG2 cells revealed marked enhancement of transcriptional activity with the T variant. The prevalence of the MTP promoter genotypes was investigated in a group of 184 healthy, middle-aged white men; the frequency of homozygosity for the MTP Ϫ493 T variant was .06 and the allele frequency of MTP Ϫ493T was .25 in the population. These homozygous subjects had a 22% lower LDL cholesterol concentration than did heterozygotes or subjects homozygous for the MTP Ϫ493 1 Functional MTP is an absolute requirement for the assembly and cellular secretion of apoB-containing lipoproteins. Cells that normally do not secrete apoB can acquire this competence if the genes encoding apoB and MTP are provided by gene transfection, as shown in HeLa cells and COS-1 cells.2,3 Conversely, if MTP activity is inhibited in cells that normally do secrete apoB-containing lipoproteins, the secretion of apoB is drastically reduced.4,5 A complete lack of MTP activity leads to abetalipoproteinemia, 6 a disease caused by mutations in the coding region of the MTP gene. 7-9The promoter region of the MTP gene is highly conserved between species and shows signs of both cell type-specific expression and response to metabolic regulators. The activity of the human MTP promoter is suppressed by insulin and enhanced by cholesterol. 10 The insulin response has been confirmed in HepG2 cells.11 It has also been shown that hamsters fed either a high-fat or a cholesterol-enriched diet have higher concentrations of MTP mRNA.Against this background we hypothesized that genetic variation in MTP expression might influence the plasma concentrations of apoB-containing lipoproteins in humans. We report herein a common functional polymorphism in the promoter region of the MTP gene, of which the rarer allele is linked to low plasma LDL cholesterol concentrations. Methods Human SubjectsA total of 184 healthy white men, aged 30 to 45 years, were recruited at random from a register containing all permanent residents of the Stockholm metropolitan area (response rate of 70%). Men with documented coronary heart disease or any other chronic disease were excluded. The mean age of the study group ...

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“…The primary gene effect was orginally thought to concern the synthesis of the protein moiety of betalipoprotein, but recent work by Lees (1967) has shown that the B-protein is present in the sera of patients and suggests that the basic abnormality concerns the formation of the complete lipoprotein macromolecule. The condition is inherited as an autosomal recessive; the heterozygotes have no clinical or haematological abnormalities, and in only one set of parents have low levels of betalipoprotein been found (Salt et al, 1960 . The lipid accumulation is due to failure of chylomicron formation; the reason for this is not clear but possibly the enzyme system responsible for betalipoprotein synthesis is also necessary for chylomicron production Although the chylomicron route of fat absorption is completely blocked, the degree of steatorrhoea is not gross, about 80% of fat being absorbed.…”

mentioning

confidence: 99%

Lipoprotein deficiency disorders

Lloyd¹

1973

Clinics in Endocrinology and Metabolism

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On Having No Beta-Lipoprotein a Syndrome Comprising a-Beta-Lipoproteinæmia, Acanthocytosis, and Steatorrhœa

Cited by 335 publications

References 17 publications

A- -lipoproteinaemia (Bassen-Kornzweig Syndrome): Report of a Case

A- -lipoproteinaemia (Bassen-Kornzweig Syndrome): Report of a Case

A Common Functional Polymorphism in the Promoter Region of the Microsomal Triglyceride Transfer Protein Gene Influences Plasma LDL Levels

Lipoprotein deficiency disorders

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