Apolipoprotein E polymorphism, serum lipids and occurrence of ‘double pre-betalipoproteinemia’ (DPBL) in subjects from two different populations

Pagnan, Antonio; Zanetti, Giulia; Bonanome, A; Biffanti, S.; Ehnholm, Christian; Keso, L.; Lukka, Matti

doi:10.1016/0021-9150(87)90004-9

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…Our data and those of Pagnan et al (45) suggest that this view may need to be reevaluated. As reported by others (9,46) and confirmed here, the concentration of apo E in blood plasma tends to be lower in subjects with an ⑀4 allele than in ⑀3 homozygotes, and a larger fraction of apo E is found in VLDL and less in HDL from subjects with an ⑀4 allele.…”

Section: Discussionsupporting

confidence: 46%

“…To our knowledge, the postprandial response of apo B100-containing TRL in individuals with an ⑀4 allele has not been reported previously. It is noteworthy, however, that "double prebetalipoproteinemia," which is characterized by the accumulation of remnant-like VLDL in postabsorptive plasma (24), has been found to be significantly more prevalent in normolipidemic Finns and hyperlipidemic Italians with apo E4/4 and E4/3 phenotypes than in those with an apo E3/3 phenotype (45). The combined data from the two populations showed that double prebetalipoproteinemia occurred in 34 out of 56 individuals (61%) with phenotypes E4/3 and E4/4, but only in 31 out of 117 individuals (27%) with phenotype E3/3.…”

Section: Discussionmentioning

confidence: 99%

“…We speculate that the apo E on chylomicron remnants of persons with an apo E4/3 phenotype may be less accessible to hepatic lipoprotein receptors than apo E from persons with an apoE3/3 phenotype. The same may apply to VLDL remnants which also appear to accumulate in persons with an apo E4/3 phenotype (45). Studies in homozygous Watanabe heritable hyperlipidemic rabbits have shown that reduced hepatic uptake of VLDL remnants is associated with increased conversion of the remnants to LDL, accounting for a substantial fraction of the increased concentration of LDL in these animals expressing an abnormal LDL receptor (56).…”

Section: Discussionmentioning

confidence: 99%

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Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.

Bergeron¹,

Havel²

1996

J. Clin. Invest.

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The postprandial responses of apo B48, B100, E and lipids in triglyceride-rich lipoproteins (TRL) to a meal containing one-third of daily energy (39% fat calories) were compared in normolipidemic young men with apo E3/3 and apo E4/3 phenotypes. After the two groups consumed a diet rich in polyunsaturated fat for 15-29 d, their postabsorptive concentrations of TRL triglycerides, apo B48, and apo B100 were virtually identical, but their postprandial responses differed. In both groups, TRL apo B48 increased at 3 h but returned to postabsorptive values at 6 h only in the apo E3/3 group; in the apo E4/3 group the concentration of apo B48 at 6 h was 80% higher than postabsorptive values. TRL apo B100 also increased at 3 h in the two groups and fell to postabsorptive values at 6 h in the apo E3/3 group but remained 51% higher than postabsorptive concentrations in the apo E4/3 group; this response was closely coupled to that of TRL cholesterol and apo E.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.

Bergeron¹,

Havel²

1996

J. Clin. Invest.

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“…In contrast, expression of apoE2, which also markedly increased hepatic VLDL-TG production, resulted in a highly significant increase in plasma triglyceride levels 3 days after vector administration, probably due to the fact that clearance of TG-rich VLDL was relatively impaired compared with apoE3. Expression of apoE4 resulted in a significantly greater increase in plasma triglycerides on day 3 compared with apoE3, consistent with the findings that humans with at least one apoE4 allele have increased plasma VLDL remnants (11) and delayed clearance of remnant lipoproteins (12), and that mice expressing apoE4 have reduced VLDL catabolism compared with mice expressing apoE3 (13).…”

Section: Discussionsupporting

confidence: 84%

Markedly increased secretion of VLDL triglycerides induced by gene transfer of apolipoprotein E isoforms in apoE-deficient mice

Tsukamoto

Maugeais

Glick

et al. 2000

Journal of Lipid Research

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Apolipoprotein E (apoE) plays a key role in the receptor-mediated uptake of lipoproteins by the liver and therefore in regulating plasma levels of lipoproteins. ApoE may also facilitate hepatic secretion of very low density lipoprotein (VLDL) triglyceride (TG). We directly tested the hypothesis that reconstitution of hepatic apoE expression in adult apoE-deficient mice by gene transfer would acutely enhance VLDL-TG production and directly compared the three major human apoE isoforms using this approach. Second generation recombinant adenoviruses encoding the three major isoforms of human apoE (E2, E3, and E4) or a control virus were injected intravenously into apoE-deficient mice, resulting in acute expression of the apoE isoforms in the liver. Despite the expected decreases in total and VLDL cholesterol levels, apoE expression was associated with increased total and VLDL triglyceride levels (E2 Ͼ E4 Ͼ E3). The increase in TG levels significantly correlated with plasma apoE concentrations. In order to determine whether acute apoE expression influenced the rate of VLDL-TG production, additional experiments were performed. Three days after injection of adenoviruses, Triton WR1339 was injected to block lipolysis of TG-rich lipoproteins and VLDL-TG production rates were determined. Mice injected with control adenovirus had a mean VLDL-TG production rate of 74 ؎ 7 mol/h/kg. In contrast, VLDL-TG production rates in apoE-expressing mice were 363 ؎ 162 mol/h/kg, 286 ؎ 175 mol/h/kg, and 300 ؎ 84 mol/h/kg for apoE2, apoE3, and apoE4, respectively. The VLDL-TG production rates in apoE-expressing mice were all significantly greater than in control mice but were not significantly different from each other. In summary, acute expression of all three human apoE isoforms in livers of apoE-deficient mice markedly increased VLDL-TG production to a similar degree, consistent with the concept that apoE plays an important role in facilitating hepatic VLDL-TG production in an isoform-independent manner. -Tsukamoto, K., C. Maugeais, J. M. Glick, and D. J. Rader. Markedly increased secretion of VLDL triglycerides induced by gene transfer of apolipoprotein E isoforms in apoE-deficient mice.

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“…Mean serum total cholesterol levels also tended to be higher in the apo E3/4 phenotype group than in the apo E3/3 phenotype group, though the difference was not quite significant at the 5~ level probably due to small sample sizes. It has been demonstrated that mean serum total cholesterol levels have a tendency to be higher in the apo E3/4 phenotype as compared with the apo E3/3 phenotype in Caucasians (Sing and Davignon, 1985;Boerwinkle et al, 1987;Pagnan et al, 1987). Considering that most of multifactorial hypercholesterolemia is not severe and that many individuals with apo E4 are normocholesterolemic, these findings suggest that the apo E4 allele acts as a polymeric gene in predisposing one to hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 99%

Association of the apolipoprotein E4 allele with hypercholesterolemia in apparently healthy male adults in Tokyo

et al. 1987

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SummaryThis study was performed to investigate whether the apolipoprotein (apo) E4 allele is associated with hypercholesterolemia in Japanese male adults in large cities. The apo E phenotypes and serum lipid levels were analyzed on 142 apparently healthy male civil servants working in Tokyo. The prevalence of hypercholesterolemia (serum total cholesterol level>250 mg/dl) were 4.7~ in 106 apo E4-absent subjects and 19.4~ in 36 apo E4-present subjects (p=0.012). The prevalence of hypercholesterolemia were 5.3~o in 94 subjects with the apo E3/3 phenotype and 20.0~ in 30 subjects with the apo E3/4 phenotype (p=0.023). In addition, mean serum total cholesterol levels were significantly higher in the apo E4-present subjects than in the apo E4-absent subjects (213_+29.1 versus 199_+36.0, p <0.05). The data suggest that the apo E4 allele is associated with hypercholesterolemia in Japanese male adults working in large cities.

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Apolipoprotein E polymorphism, serum lipids and occurrence of ‘double pre-betalipoproteinemia’ (DPBL) in subjects from two different populations

Cited by 7 publications

References 32 publications

Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.

Prolonged postprandial responses of lipids and apolipoproteins in triglyceride-rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.

Markedly increased secretion of VLDL triglycerides induced by gene transfer of apolipoprotein E isoforms in apoE-deficient mice

Association of the apolipoprotein E4 allele with hypercholesterolemia in apparently healthy male adults in Tokyo

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